Hydrophobic synthetic melanin nanoparticles

Abstract

Embodiments disclosed herein include materials and formulations comprising functionalized artificial melanin nanoparticles, wherein each functionalized artificial melanin nanoparticle comprises a surface functionalized with a modifying agent via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; and the linker group is an amine group. Embodiments also include methods of healing skin damage using the disclosed formulations.

Description

Detailed Description of the Invention

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS]

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 418,257, filed October 21, 2022, the entire contents of which are incorporated herein by reference.

[0002] [STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT] This application was made with government support under Grant No. AR079795 awarded by the National Institutes of Health and Grant No. FA9550-18-1-0142 awarded by the Air Force Office of Scientific Research. The government has certain rights in this invention.

[0003] [Background of the invention]

[0003] Melanin is a natural pigment found in skin and hair that plays a major role in UV radiation protection through absorption of incident radiation and radical scavenging activity. Synthetic or artificial melanin materials, obtained via oxidative polymerization of inexpensive monomers, successfully replicate these properties and avoid the yield and purity problems associated with natural extraction. The resulting materials are typically hydrophilic, which limits the applications of these materials outside of aqueous systems.

[0004] [Summary of the Invention]

[0004] The materials and methods disclosed herein provide surface-modified or functionalized artificial melanin materials, such as artificial melanin nanoparticles, optionally hydrophobic artificial melanin nanoparticles, methods for preparing them, formulations of these materials, and methods for using these materials and formulations to treat subjects, such as to promote skin healing. The methods disclosed herein for functionalizing artificial melanin nanoparticles provide a scheme for a wide range of functionalization or property modification of artificial melanin materials, including, but not limited to, increasing their hydrophobicity.

[0005]

[0005] Aspects disclosed in the present specification include a functionalized artificial melanin material comprising a surface functionalized with a modifying agent via a linker group, wherein the modifying agent comprises a linker group and a functional group bonded to the linker group; and the linker group is a nucleophilic group.

[0006]

[0006] Embodiments disclosed herein include a melanin-containing formulation comprising one or more solvents (optionally one or more hydrophobic solvents); a functionalized artificial melanin material dispersed in the one or more solvents; the functionalized artificial melanin material comprising a surface functionalized with a modifying agent via a linker group; the modifying agent comprising a linker group and a functional group bonded to the linker group; and the linker group being a nucleophilic group.

[0007]

[0007] Aspects disclosed herein include a method for treating a subject, comprising the steps of: topically administering a melanin formulation to damaged skin of the subject; the functionalized artificial melanin material comprising a surface functionalized with a modifying agent via a linker group; the modifying agent comprising a linker group and a functional group bonded to the linker group; the linker group being a nucleophilic group; the melanin formulation comprising one or more solvents (optionally one or more hydrophobic solvents) and the functionalized artificial melanin material dispersed in the one or more solvents (optionally one or more hydrophobic solvents); the administered functionalized artificial melanin material comprising extracellular functionalized artificial melanin material to the damaged skin; and promoting healing of the damaged skin via at least the extracellular functionalized artificial melanin material; the step of promoting skin healing comprising at least a portion of the extracellular artificial melanin material exerting therapeutic extracellular activity.

[0008]

[0008] Aspects disclosed herein include a method for preparing a functionalized artificial melanin material, comprising the steps of: providing non-functionalized artificial melanin nanoparticles; and exposing the non-functionalized artificial melanin nanoparticles to a precursor of a modifying agent for a limited time, wherein the exposing step includes conjugating the non-functionalized artificial melanin nanoparticles with the precursor, thereby forming functionalized artificial melanin nanoparticles having the modifying agent, wherein the functionalized artificial melanin nanoparticles comprise a surface functionalized with the modifying agent via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; and the linker group is a nucleophilic group.

[0009]

[0009] Aspects disclosed herein include a functionalized artificial melanin material, including a surface functionalized with a modifier via a linker group; the modifier comprising a linker group and a functional group attached to the linker group; and the linker group being an amine group. Optionally, the material includes functionalized artificial melanin nanoparticles, each of which independently comprises a surface functionalized with a modifier via a linker group.

[0010]

[0010] Aspects disclosed herein include materials comprising functionalized artificial melanin nanoparticles, wherein each functionalized artificial melanin nanoparticle comprises a surface or portion functionalized with a modifying agent via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; and the linker group is an amine group. Optionally, the linker group is attached to each particle via a single or double bond. Optionally, the linker group is a primary amine group. Optionally, the linker group has the formula FX1A or FX1B: [ka] It is characterized by: Optionally, the modifying agent has the formula FX2A or FX2B: [ka] (wherein X is a functional group) Optionally, each linker group is independently attached to a phenyl group or a quinone of a respective artificial melanin nanoparticle. Optionally, the modifier attached to each functionalized artificial melanin nanoparticle is the product of a Michael addition or via a Schiff base reaction. Optionally, the functionalized surface is at least partially an outer surface and / or at least partially an inner pore surface of each artificial melanin nanoparticle. Optionally, the artificial melanin nanoparticle is characterized as polydopamine and / or allomelanin.

[0011] Aspects disclosed herein further include a dispersion comprising one or more solvents; and a material (or functionalized artificial melanin nanoparticles thereof) according to any one or more embodiments disclosed herein in the one or more solvents. Optionally, the dispersion (or material thereof) is characterized by a contact angle of at least 90°, optionally at least 110°, and optionally at least 120°. As used herein, a contact angle greater than 90° is defined as hydrophobic. In embodiments, a sessile drop measurement using water as the solvent is a sufficient measure of hydrophobicity. Optionally, the dispersion (or material thereof) is characterized by a pH selected from the range of 3 to 11.

[0012] Aspects disclosed herein further include a thin film of a material (or functionalized artificial melanin nanoparticles thereof) according to any one or more embodiments disclosed herein. Optionally, the thin film has or exhibits structural color. Optionally, the thin film has one or more monolayers of functionalized artificial melanin nanoparticles. Optionally, the thin film has one, two, three, or four monolayers of functionalized artificial melanin nanoparticles.

[0013] Aspects disclosed herein further include a method for preparing a material (or functionalized artificial melanin nanoparticles thereof) according to any one or more embodiments disclosed herein, comprising: providing non-functionalized artificial melanin nanoparticles; and exposing the non-functionalized artificial melanin nanoparticles to a precursor of a modifying agent for a limited time, where the exposing step comprises conjugating the non-functionalized artificial melanin nanoparticles with the precursor, thereby forming functionalized artificial melanin nanoparticles bearing the modifying agent. In embodiments, the non-functionalized artificial melanin nanoparticles do not comprise a modifying agent according to an embodiment disclosed herein or have not been pre-functionalized / pre-modified by the addition / conjugation of a modifying agent (or a precursor thereof) to the artificial melanin nanoparticles. Optionally, the non-functionalized artificial melanin nanoparticles are hydrophilic and dispersed in an aqueous solution. Optionally, the conjugating comprises rendering the functionalized artificial melanin nanoparticles more hydrophobic (e.g., having a higher contact angle) than the provided non-functionalized artificial melanin nanoparticles. Optionally, the method includes aging or oxidizing the non-functionalized artificial melanin nanoparticles, optionally to form or increase the content of quinones in the non-functionalized artificial melanin nanoparticles.

[0014] While not wishing to be bound by any particular theory, there may be discussion herein of beliefs or understandings of underlying principles relating to the devices and methods disclosed herein. It is recognized that regardless of the ultimate correctness of any mechanistic explanation or hypothesis, certain embodiments of the present invention may nevertheless be effective and useful. [Brief explanation of the drawings]

[0015] [Figure 1A] 1 shows the synthesis and post-synthetic modifications of AMNPs. FIG. 2 shows the schematic synthesis of fresh, aged, and modified AMNPs. [Figure 1B]Figure 1 shows the synthesis and post-synthetic modification of AMNPs. TEM images of solid AMNPs (S-AMNPs), walnut AMNPs (W-AMNPs), hollow AMNPs (H-AMNPs), and lace-like AMNPs (L-AMNPs). Scale bar 200 nm. [Figure 2A] 1 shows the synthesis of AMNP-NMe2. Post-synthetic modification of AMNP with DMEN and a TEM image of the resulting S-AMNP-NMe2. Scale bar 200 nm. [Figure 2B] 1 shows the synthesis of AMNP-NMe2. XPS (i) survey spectrum, (ii) N1s spectrum of S-AMNP; (iii) survey spectrum, (iv) N1s spectrum of S-AMNP-NMe2. [Figure 2C] Figure 1 shows the synthesis of AMNP-NMe2. (i) Hydrodynamic diameter and (ii) Zeta potential of S-AMNP and S-AMNP-NMe2 in Mili-Q water at different pH values. [Figure 2D] 1 shows the synthesis of AMNP-NMe2. 2 shows STEM-EDX mapping analysis of S-AMNP-NMe2. Scale bar 200 nm. [Figure 3A] Figure 1 shows the synthesis of hydrophobic allomelanin. Post-synthetic modification of AMNPs using C6-NH2 and C18-NH2, and a TEM image of the resulting S-AMNP-C18. Scale bar 200 nm. [Figure 3B] 1 shows the synthesis of hydrophobic allomelanins, and 2 shows the XPS survey spectra and N1s spectra of S-AMNP-C6 and S-AMNP-C18. [Figure 3C] Figure 1 shows the synthesis of hydrophobic allomelanins: (i) Hydrodynamic diameters of S-AMNP, S-AMNP-C6, and S-AMNP-C18 in EtOH; (ii) FTIR spectra of S-AMNP, S-AMNP-C6, and S-AMNP-C18. [Figure 3D]Figure 1 shows the synthesis of hydrophobic allomelanins. Figure 2 shows the partitioning of S-AMNP, S-AMNP-C18, and S-AMNP-C6 in water and different solvents (CH2Cl2, CHCl3, and ethyl acetate). [Figure 3E] Figure 1 shows the synthesis of hydrophobic allomelanins. Figure 2 shows static water contact angle data for drop-cast S-AMNP, S-AMNP-C18, and S-AMNP-C6 films. [Figure 4A] Figure 1 shows the air / water interfacial self-assembly of hydrophobic allomelanins. Figure 2 shows the general procedure for air / water interfacial self-assembly. [Figure 4B] Figure 1 shows the air / water interfacial self-assembly of hydrophobic allomelanin. Top-view SEM images of S-AMNP-C18 monolayers. Scale bars: (i) 1 μm, (ii) 500 nm, and (iii) the corresponding FFT images. [Figure 4C] Figure 1 shows the air / water interfacial self-assembly of hydrophobic allomelanin. Figure 2 shows the reflectance spectra of S-AMNP-C18 for different numbers of layers (L1, L2, L3, L4). The experimental reflectance curve is the average of five locations on the film, and the shaded area represents the error bar as the standard deviation. [Figure 4D] Figure 1 shows the air / water interfacial self-assembly of hydrophobic allomelanins. Cross-sectional SEM images of (i) L1, (ii) L2, (iii) L3, and (iv) L4 of S-AMNP-C18 and corresponding optical microscope images. [Figure 4E] Figure 1 shows the air / water interfacial self-assembly of hydrophobic allomelanins. Cross-sectional SEM images of (i) L1, (ii) L2, (iii) L3, and (iv) L4 of W-AMNP-C18 and corresponding optical microscope images. [Figure 4F] Figure 1 shows the air / water interfacial self-assembly of hydrophobic allomelanins. Cross-sectional SEM images of (i) L1, (ii) L2, (iii) L3, and (iv) L4 of H-AMNP-C18 and corresponding optical microscope images. [Figure 4G]Figure 1 shows the self-assembly of hydrophobic allomelanins at the air / water interface. Cross-sectional SEM images of (i) L1, (ii) L2, (iii) L3, and (iv) L4 of L-AMNP-C18 and corresponding optical microscope images. Scale bar 500 nm. [Figure 5] The top diagram shows how functionalization (or "modification") according to embodiments herein transforms hydrophilic artificial melanin nanoparticles into hydrophobic artificial melanin nanoparticles, as evidenced by the increase in contact angle from less than 90° to more than 90°. The bottom diagram shows the self-assembly of a monolayer of functionalized artificial melanin nanoparticles, where L1-L4 represent 1, 2, 3, or 4 layers of nanoparticles, respectively. [Figure 6] Figure 1 shows the synthesis and post-synthetic modification of AMNPs. (A) Upon addition of an oxidizing agent, dimerization of 1,8-DHN leads to the formation of three types of DHN dimers: 2-2' dimer, 4-4' dimer, and 2-4' dimer; (B) further oxidation results in DHN oligomers, which self-assemble to form fresh AMNPs; (C) spontaneous oxidation of fresh AMNPs produces aged AMNPs, which contain DHN oligomers with a higher degree of polymerization, more cross-linked structures, and more quinone moieties; (D) post-synthetic modification results in AMNP-NHR, in which amine molecules are conjugated to the particles via either Michael addition or Schiff base reaction. [Figure 7A] Figure 1 shows UV-Vis of S-AMNP over time. Figure 1 shows the time course of absorbance of S-AMNP at 0 days, 4 days, 9 days, 14 days, 24 days, 42 days, and 7 months after synthesis. [Figure 7B] Photographs of S-AMNPs in Milli-Q water at a concentration of 4 mg / mL at 0 and 14 days after the initial reaction. [Figure 8] FIG. 1 shows the calculation of the ratio of DMEN to DHN structural units. [Figure 9A] FIG. 1 shows a nitrogen isotherm at 77 K. [Figure 9B] FIG. 1 shows the pore size distribution of S-AMNP and S-AMNP-NMe2. [Figure 10]STEM-EDX mapping analysis of resin-embedded and 50-nm-thick sliced ​​S-AMNP-NMe2. Scale bar: 100 nm. [Figure 11A] XPS (i) survey spectrum, (ii) N1s spectrum of W-AMNP; (iii) survey spectrum, (iv) N1s spectrum of W-AMNP-NMe2. [Figure 11B] XPS (i) survey spectrum, (ii) N1s spectrum of H-AMNP; (iii) survey spectrum, (iv) N1s spectrum of H-AMNP-NMe2. [Figure 11C] XPS (i) survey spectrum, (ii) N1s spectrum of L-AMNP; (iii) survey spectrum, (iv) N1s spectrum of L-AMNP-NMe2. [Figure 12A] Figure 1 shows the hydrodynamic diameters of W-AMNP (179.4 nm, PDI = 0.054) and W-AMNP-NMe2 (213.4 nm, PDI = 0.133). [Figure 12B] FIG. 1 shows the hydrodynamic diameters of H-AMNP (206.8 nm, PDI=0.195) and H-AMNP-NMe2 (307.5 nm, PDI=0.324). [Figure 12C] FIG. 1 shows the hydrodynamic diameters of L-AMNP (200.7 nm, PDI=0.205) and L-AMNP-NMe2 (254.1 nm, PDI=0.202). [Figure 12D] FIG. 1 shows the zeta potential of AMNP and AMNP-NMe2 in Mili-Q water. [Figure 13] FIG. 1 shows UV-Vis of S-AMNP, S-AMNP-C6, and S-AMNP-C18 in EtOH. [Figure 14A] FIG. 1 shows a nitrogen isotherm at 77 K. [Figure 14B] FIG. 1 shows the pore size distributions of S-AMNP, S-AMNP-C6, and S-AMNP-C18. [Figure 15]Figure 1 shows STEM-EDX mapping analysis of S-AMNP-C18. Scale bar 200 nm. [Figure 16] FIG. 1 shows the partitioning of S-AMNP, S-AMNP-C6, and S-AMNP-C18 in water and different solvents (CH2Cl2, CHCl3, toluene, ethyl acetate, hexane, and cyclohexane). [Figure 17] FIG. 1 shows the partitioning of S-AMNP, S-AMNP-C6, and S-AMNP-C18 in water and toluene, hexane, and cyclohexane. [Figure 18A] 1 shows XPS of modified S-AMNP, and 2 shows survey and N1s spectra of AMNP-C5-OH modified with 5-amino-1-pentanol. [Figure 18B] 1 shows XPS of modified S-AMNP, and survey and N1s spectra of AMNP-tBu modified with tert-butylamine. [Figure 18C] 1 shows XPS of modified S-AMNP, and 2 shows survey and N1s spectra of AMNP-C10-OH modified with 10-amino-1-decanol. [Figure 18D] 1 shows XPS of modified S-AMNP, and 2 shows survey and N1s spectra of AMNP-C6-NH2 modified with 1,6-hexanediamine. [Figure 18E] 1 shows XPS of modified S-AMNP. 2 shows survey, N1s, and F1s spectra of AMNP-F modified with 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononylamine. [Figure 19A] FIG. 1 shows XPS survey spectra of (i) W-AMNP-C18, (ii) H-AMNP-C18, and (iii) L-AMNP-C18. [Figure 19B] FIG. 1 shows XPS N1s spectra of (i) W-AMNP-C18, (ii) H-AMNP-C18, and (iii) L-AMNP-C18. [Figure 20A]Top-view SEM image of a W-AMNP-C18 monolayer. Scale bar: 500 nm. [Figure 20B] Top-view SEM image of a H-AMNP-C18 monolayer. Scale bar: 500 nm. [Figure 20C] Top-view SEM image of an L-AMNP-C18 monolayer. Scale bar: 500 nm. [Figure 21] 1 is an AFM image of a W-AMNP-C18 monolayer showing the nanoparticle outline. [Figure 22A] Figure 1 shows the reflectance spectra of monolayer (L1), bilayer (L2), trilayer (L3), and tetralayer (L4) films formed with W-AMNP-C18. The experimental reflectance curves are the average of five locations on the film, and the shaded areas represent the error bars as standard deviations. [Figure 22B] Figure 1 shows the reflectance spectra of monolayer (L1), bilayer (L2), trilayer (L3), and tetralayer (L4) films formed with H-AMNP-C18. The experimental reflectance curves are the average of five locations on the film, and the shaded areas represent the error bars as standard deviations. [Figure 22C] Figure 1 shows the reflectance spectra of monolayer (L1), bilayer (L2), trilayer (L3), and tetralayer (L4) films formed with L-AMNP-C18. The experimental reflectance curves are the average of five locations on the film, and the shaded areas represent the error bars as standard deviations. [Figure 23A] 1A-1C are TEM micrographs verifying the spherical morphology of hydrophobic melanin nanoparticles AMNP-C18. [Figure 23B] TEM micrographs verifying the spherical morphology of hydrophobic melanin nanoparticles. [Figure 24A] Figure 1 shows the FTIR spectra of AMNPs and comparison of AMNPs with hydrophobic AMNPs. New peaks appear at 2920 cm and 2850 cm, corresponding to alkane C-H bond stretching, indicating the attachment of alkylamines to the surface of the particles. [Figure 24B]Figure 1 shows the FTIR spectra of PDA, PDA and PDA-C18 showing peaks at 2920 cm and 2850 cm corresponding to alkane C-H bond stretching. [Figure 25A] FIG. 1 shows the DPPH radical scavenging assay of AMNPs. [Figure 25B] FIG. 1 shows DPPH radical scavenging assay of PDA. [Figure 26] FIG. 1 shows a qualitative assessment of the solubility of synthetic melanin nanoparticles in Aquaphor and petrolatum. [Figure 27A] FIG. 1 shows the solubility of PDA in squalane and squalene. [Figure 27B] FIG. 1 shows the solubility of PDA-C18 in squalane and squalene. [Figure 28A] FIG. 1 shows a chemical schematic of functionalization of artificial melanin nanoparticles, illustrating that conjugation (or functionalization) of a modifier to a melanin nanoparticle according to embodiments herein can occur by Michael addition and / or Schiff base reaction according to embodiments herein, such that a linker group, such as an amine group, can be attached to the nanoparticle, or naphthalene or its aromatic group, for example, via a single or double bond. [Figure 28B] FIG. 1 shows a chemical schematic of functionalization of artificial melanin nanoparticles, illustrating that conjugation (or functionalization) of a modifier to a melanin nanoparticle according to embodiments herein can occur by Michael addition and / or Schiff base reaction according to embodiments herein, such that a linker group, such as an amine group, can be attached to the nanoparticle, or naphthalene or its aromatic group, for example, via a single or double bond. [Figure 29A] Figure 1 shows XPS of modified S-AMNP. Figure 2 shows survey and N1s spectra of AMNP-mPEG-550 modified with mPEG-NH2 (MW 550). [Figure 29B]Figure 1 shows XPS of modified S-AMNP. Figure 2 shows survey and N1s spectra of AMNP-mPEG-2000 modified with mPEG-NH2 (MW 2000). [Figure 30] FIG. 1 shows the FTIR spectra of S-AMNP-mPEG-550 and S-AMNP-mPEG-2000. [Figure 31] 1 is a table showing the thickness of AMNP-C18 thin films obtained from SEM. [Figure 32] FIG. 1 shows reflectance spectra visualized on the CIE 1931 chromaticity diagram for human color vision for different melanin structures and layer numbers (filled circles: S-AMNP-C18, asterisks: W-AMNP-C18, open circles: H-AMNP-C18, filled triangles: L-AMNP-C18). [Figure 33] Figure 1 shows an overview of cellular and molecular markers after NM exposure (injury phase), and shows that the situation changes during the recovery phase. [Figure 34A] 1 shows the synthesis of 10 candidate intervening molecules (SMPs). FIG. 2 shows a generalized scheme for polydopamine (PDA) preparation and modification. [Figure 34B] 1 shows the synthesis of 10 candidate intercalators (SMPs). Core = active SMP component. Shell = covalent surface modification. [Figure 34C] 1 shows the synthesis of 10 candidate interventions (SMPs), TEM images and zeta (z) potentials of five PDA-based SMPs. [Figure 34D] 1 shows the synthesis of 10 candidate interventions (SMPs). FIG. 2 shows a generalized scheme for allomelanin (ANP) preparation and further modification. [Figure 34E] 1 shows the synthesis of 10 candidate interventions (SMPs).FIG. 2 shows TEM images and zeta potentials of five ANP-based SMPs. [Figure 35] 1 shows a cross section of healthy human skin to which a PDA has been applied, showing that the PDA can be seen within and above the stratum corneum (arrows). [Figure 36]FIG. 1 illustrates the workflow setup of human skin explants for nitrogen mustard exposure and SMP treatment. [Figure 37A] H&E shows the extent of subepidermal blisters and necrotic (dyskeratinized) keratinocytes (black arrows). NTC = non-NM treated control. Scale bar = 100 μm. [Figure 37B] Figure 1 shows severity as scored by a blinded dermatopathologist.Figure 2 shows human explants (n=10) exposed to NM followed by intervention with vehicle or PDA. [Figure 37C] Figure 1 shows severity as scored by a blinded dermatopathologist.Figure 2 shows human explants (n=10) exposed to NM followed by intervention with vehicle or PDA. [Figure 37D] Demographic information: All 10 participants were female, age range 25-51 years, median age ± sd was 36 ± 6.4 years. [Figure 38A] Biomarker validation in human skin explants: clinical trial study of in vivo NM exposure correlates with upregulation of multiple inflammatory pathways. Confirmed IL-8 protein and quantitative protein Ab array (T-test, n=6-7). [Figure 38B] Biomarker validation in human skin explants: clinical trial study of in vivo NM exposure correlates with upregulation of multiple inflammatory pathways. ICAM1 protein confirmed and quantitative protein Ab array (T-test, n=6-7). [Figure 38C] Figure 1 shows biomarker validation in human skin explants: clinical trial study of in vivo NM exposure correlates with upregulation of multiple inflammatory pathways. Figure 2 shows ccl20 gene expression confirmed by qRT-PCR (T-test, n=7). [Figure 38D]Figure 1 shows biomarker validation in human skin explants: clinical trial study of in vivo NM exposure correlates with upregulation of multiple inflammatory pathways. Figure 2 shows osm gene expression confirmed by qRT-PCR (T-test, n=7). [Figure 39] FIG. 1 shows small 40 nm PDA particles. [Figure 40A] Figure 1 shows that PDA intervention in NM-exposed mice significantly downregulated apoptosis as quantified by TUNEL. [Figure 40B] Figure 1 shows that PDA intervention in NM-exposed mice significantly downregulated the expression of MMP9. [Figure 40C] Figure 1 shows that PDA intervention in NM-exposed mice significantly downregulated phosphorylated ERK1 / 2. [Figure 40D] Figure 1 shows that PDA intervention in NM-exposed mice significantly downregulated and increased the early wound healing angiogenesis marker CD31. [Figure 41A] Figure 1 shows skin wounds after NM exposure. Figure 2 shows that PDA intervention significantly reduces the initial wound area reduction on days 2 and 3 (n=16). [Figure 41B] Figure 1 shows skin wounds after NM exposure, resulting in smaller wounds at 14 days. [Figure 41C] Figure 1 shows skin wounds after NM exposure, NM causes deep damage to the skin, and PDA intervention limits the depth of the damage. [Figure 41D] FIG. 1 shows that immunophenotyping of wounds and corresponding splenic populations shows an increase in reparative immune cells. [Figure 42A] This figure shows that SOD activity was reduced after NM exposure (**p<0.01) and rescued by PDA (*p<0.05) (n=3-7). [Figure 42B]FIG. 1 shows that the SOD inhibitor ATN-224 abolished the previously observed positive effects of PDA on wound healing and apoptosis. [Figure 42C] FIG. 1 shows that the SOD inhibitor ATN-224 abolished the previously observed positive effects of PDA on wound healing and apoptosis. [Figure 43A] Figure 1 shows re-epithelialization and epidermal recovery. Figure 2 shows the percentage of eschar detachment plotted (n=10). [Figure 43B] Figure 1 shows re-epithelialization and epidermal recovery.Figure 2 shows wound histology on day 16. [Figure 43C] Figure 1 shows re-epithelialization and epidermal recovery.PDA intervention showed significantly reduced phospho-JNK activation (p<0.05, n=3). [Figure 43D] Figure 1 shows re-epithelialization and epidermal recovery, and smaller focal scars measured by Masson's trichome staining. [Figure 44A] Figure 1 shows a pilot study of UV-induced blisters in vivo in a porcine model (black arrows point to the area of ​​interest). UV H&E shows complete subepidermal blisters. [Figure 44B] Figure 1 shows a pilot study of UV-induced blisters in vivo in a porcine model (black arrows point to areas of interest). Figure 2 shows that PDA in UV+water has surface damage. [Figure 44C] Figure 1 shows a pilot study of UV-induced blisters in vivo in a pig model (black arrows point to areas of interest). Figure 2 shows that PDA in UV + Aquaphor® has relatively mild epidermal damage. [Figure 44D] Figure 1 shows a pilot study of UV-induced blisters in vivo in a pig model (black arrows point to areas of interest). Figure 2 shows that PDA-C18 in UV + Aquaphor® has superficial epidermal damage without subepidermal blisters. [Figure 44E] Figure 1 shows a pilot study of UV-induced blistering in vivo in a porcine model. Skin redness measurements using a Chromameter on day 2 after the onset of sunburn (p=0.02, n=5). [Figure 44F] FIG. 1 shows the solubility of modified PDA SMPs. [Figure 44G] FIG. 1 illustrates the ability to formulate low concentrations into different skin vehicles. [Figure 45]

[0023] Figure 1 shows the nitrogen mustard porcine model.

[0024] Figure 2 shows the skin progression of redness and crusting.

[0025] H&E contrasts normal baseline skin with NM-induced full thickness necrosis. [Figure 46]

[0023] Figure 1 shows the study randomization schedule for testing SMP in a porcine model. Numbers indicate animals. Randomization is based on 6 test spots per animal. [Figure 47] Figure 1 shows the 15-point histopathological scoring tool adapted from Barillo et al. (2020). Figure 2 shows the criteria used for FDA approval of Silverlon. [Figure 48A] FIG. 10 is a diagram showing details of a PDA. [Figure 48B] This is a diagram showing the details of the PDA-C18. [Figure 49A] FIG. 1 shows skin reddening after UV exposure with application of formulations to the skin as labeled, where topical application of 2% w / w PDA-C18 in Aquaphor® resulted in a decrease in the percentage of reddening over the course of the experimental period, also showing significance in the reduction of reddening compared to the vehicle control. [Figure 49B] FIG. 1 shows skin redness in the case of prophylaxis involving application of formulations to the skin as labeled, where topical application of 2% w / w PDA-C18 behaves like a sunscreen and performs similarly to the control sunscreen (SPF 60) in that it successfully prevents UV-B-induced damage. [Figure 50A]1 shows a reaction scheme for forming PDA-C18 according to an embodiment of the present disclosure. FIG. 2 shows a modifier attached to a melanin nanoparticle. [Figure 50B] 1 shows a reaction schematic for forming PDA-C18 according to an embodiment of the present disclosure. FIG. 2 shows a chemical linkage scheme between some monomer units of a PDA particle and a modifier. [Figure 51A] FIG. 1 shows a reaction scheme for forming functionalized artificial PDA nanoparticles according to embodiments herein. [Figure 51B] 1 shows a reaction scheme for forming functionalized artificial ANP nanoparticles according to embodiments herein. As used herein, "ANP" and "AMNP" are equivalent and interchangeable and refer to artificial allomelanin nanoparticles. [Figure 52] Figure 1 shows an in vivo mouse skin injury / chemical burn model. Figure 2 shows that PDA-C6 significantly downregulates key factors in inflammation and tissue destruction. Figure 3 shows that PDA-C6 is distinguished from PDA by its ability to downregulate CXCL1 (n=3, P, 0.041), a potent cytokine that is a chemotactic signal that recruits neutrophils. Figure 4 shows that neutrophil activity is rapid within the skin, leading to destruction of surrounding tissue. Figure 5 shows that intervention with PDA-C6 provides an additional benefit in the down-selection process. [Figure 53] Figure 1 shows an in vivo mouse skin injury / chemical burn model. PDA-C18 inhibits a key factor in collagen degradation, which is important in tissue repair, recovery, and scarring. Figure 2 shows that PDA-C18 is unique in its ability to suppress MMP3, a matrix metalloproteinase enzyme (n=3, P<0.0002). MMP3 plays an important role in inflammation-mediated collagen degradation in the skin. Downregulation of MMP3 is important for skin recovery, repair, and scarring. [Figure 54A]Figure 1 shows an in vivo mouse skin injury / chemical burn model: PDA-C18 significantly down-regulates genes involved in excess collagen and scarring. Figure 2 shows that PDA-C18 down-regulates Col3a1, the gene encoding collagen III. Collagen III is significantly increased in hypertrophic scars and even more so in keloids. Figure 3 shows that PDA-C18 significantly reduced Col3a1 compared to controls (n=3, p=0.003). The model involves exposing animals to a severe, blistering dose of nitrogen mustard as a chemical irritant, resulting in swelling, redness, and crusting. [Figure 54B] Figure 1 shows an in vivo mouse skin injury / chemical burn model: PDA-C6 significantly down-regulates genes involved in excess collagen and scarring. Figure 2 shows that PDA-C6 down-regulates Col3a1, the gene encoding collagen III. Collagen III is significantly increased in hypertrophic scars and even more so in keloids. Figure 3 shows that PDA-C6 significantly reduced Col3a1, independent of vehicle-water (n=3, p=0.009) or Aquaphor ointment (n=3, p=0.039). The model involves exposure of animals to a severe, blistering dose of nitrogen mustard as a chemical irritant, resulting in swelling, redness, and crusting. [Figure 55] Figure 1 shows that PDA-C6 reduces skin wound size in a mouse skin injury / chemical burn model in vivo. PDA-C6 in water vehicle and PDA-C6 in Aquaphor® ointment (n=3, p=0.02) reduced wound size after severe burn injury measured on day 3. The model involves exposure of animals to a severe, blistering dose of nitrogen mustard as a chemical irritant, resulting in swelling, redness, and scab formation. The model involves induction of a well-established burn on day 2 with a distinct scab. The transition from day 2 to day 3 is a critical early time point for observing wound reduction. [Figure 56]Figure 1 shows an in vivo mouse skin injury / chemical burn model: PDA-C18 in Aquaphor® and PDA-C6 in Aquaphor® significantly reduced the skin swelling thickness response. Figure 1 shows that PDA-C6 and PDA-C18 significantly reduced skin thickness by day 3 after wound initiation. The model involves exposure of animals to a severe, blistering dose of nitrogen mustard as a chemical irritant, resulting in swelling, redness, and scab formation. Note: PDA-C6 in Aquaphor® vs. control (n=3, p=0.03); PDA-C18 in Aquaphor® vs. control (n=3, p<0.01); PDA in Aquaphor® vs. control (n=3, p<0.01). [Figure 57] Figure 1 shows an in vivo mouse skin injury / chemical burn model: PDA-C6 in a water-based vehicle significantly reduces the skin swelling thickness response. Figure 1 shows that PDA-C6 in water significantly reduced skin thickness by day 3 after wound initiation. The model involves exposure of animals to a severe blistering dose of nitrogen mustard as a chemical irritant, resulting in swelling, redness, and scab formation. Note: PDA-C6 in water vs. control (n=3, p=0.01). [Figure 58] Figure 1 shows an in vivo mouse skin injury / chemical burn model: Histology of PDA-C18 and PDA-C6 tissues demonstrates less skin tissue swelling and the extent of inflammatory cells. In this model, mice are exposed to a severe, blistering dose of nitrogen mustard (NM) as a chemical irritant, resulting in swelling, redness, and scab formation. On day 3, animals are sacrificed and skin is harvested. Shown here are hematoxylin and eosin stains. Histology demonstrates a significant increase in inflammatory cells within all layers of the skin, skin swelling, and reactive hyperplasia following NM exposure. Figure 2 shows that intervention with PDA-C6 in water, PDA-C6 in Aquaphor®, or PDA-C18 in Aquaphor® demonstrates a reduction in inflammatory cell infiltrate, less reactive hyperplasia, and tissue edema. All images are full scans with the wound edge facing left. [Figure 59A] 1 shows that skin inflammation is directly related to the amount of inflammation in the skin. In post-UV exposure conditions, topical application of 2% w / w PDA-C18 in Aquaphor® resulted in a decrease in the percentage of redness over the course of the experimental period, and also showed significance in the reduction of redness compared to the vehicle control. [Figure 59B] Figure 60A-C shows that skin inflammation is directly related to the amount of inflammation in the skin. In the case of prophylaxis, 2% w / w PDA-C18 behaves like a sunscreen and performs similarly to a control sunscreen (SPF 60) in that it successfully prevents UV-B-induced damage. This is supported through analysis of histology samples, as shown in Figures 60A-C, where prophylactic application of PDA-C18 results in healthy-looking skin. [Figure 60A] FIG. 1 shows a histology showing skin after UV exposure without treatment or protection. [Figure 60B] FIG. 1 shows histology showing skin after UV exposure for PDA-C18 in Aquaphor®. [Figure 60C] FIG. 1 shows a histology diagram showing skin after UV exposure to sunscreen.

[0016] [Chemical Compounds and Nomenclature]

[0075] Generally, the terms and phrases used herein have their art-recognized meanings, which can be found by reference to standard textbooks, journal references, and contexts known to those skilled in the art. The following definitions are provided to clarify their specific use in the context of the present invention.

[0017]

[0076] The term "damaged skin" refers to a region of skin of a living subject, the region comprising damaged skin tissue. Damaged skin may optionally comprise free radical species, including extracellular free radical species. Damaged skin may optionally comprise inflammation. Damaged skin may optionally comprise a closed wound. Damaged skin may optionally comprise a stratum corneum. Damaged skin may optionally comprise one or more visible blisters, microscopic vesicles, and separation of the epidermis from the dermis. The damaged skin may optionally comprise thermally induced damage, chemically induced damage, UV induced damage, mechanical abrasion damage, infectious cellulitis induced damage, and / or radiation induced damage.

[0018]

[0077] The term "closed wound" is intended to be consistent with terminology in the art, particularly in the field of biomedical science, and generally refers to a wound to which remnants of superficial skin remain attached. Generally, a closed wound may, but need not, optionally include one or more small openings and / or compromised lesion areas while still having remnants of superficial skin attached. For example, a lesion formed by excisional biopsy of skin generally can be characterized as an open wound rather than a closed wound. For example, an open ulcer bed can be characterized as an open wound rather than a closed wound.

[0019]

[0078] Skin scarring or scarred skin refers to the same term as understood by those skilled in the art of dermatology. In particular, in embodiments, it refers to skin having altered, abnormal-looking skin, raised skin, visible subsurface palpable nodules, altered skin color that does not resemble adjacent normal, unaffected skin, altered shiny skin, altered skin without visible hair, and / or altered skin that is less mobile and flexible compared to unaffected skin.

[0020]

[0079] The term "therapeutic extracellular activity" refers to a therapeutic activity or function that occurs extracellularly and / or involves at least one extracellular species that directly exerts or is directly involved in the activity. The term "therapeutic extracellular activity" is intended to be understood by those skilled in the art of biomedical science. For example, therapeutic extracellular activity can refer to extracellular melanin material exerting or participating in a therapeutic activity. For example, therapeutic extracellular activity can refer to an extracellular species affecting a therapeutic effect. For example, therapeutic extracellular activity can refer to extracellular melanin material exerting or participating in a therapeutic activity on or with extracellular species such as, but not limited to, extracellular free radical species, extracellular inflammatory factor(s), and / or extracellular enzymatic factor(s). A therapeutic activity or function is an activity or function that has a therapeutic or pharmaceutical effect or benefit, such as for the treatment or amelioration of an injury, wound, tissue damage, disease, pathology, or condition. Therapeutic activity or function may include one or more chemical and / or physical processes, such as one or more chemical reactions or transformations, one or more physical transformations, covalent or non-covalent associations or interactions between species, adsorption, etc. Therapeutic activity may include, but is not limited to, processes such as quenching or sequestration, adsorption, regulation, such as downregulation of gene expression, inhibition of activity or function, of one or more species, such as, but not limited to, proteins, enzymes, or gene expression factors, and any combination thereof. The term "therapeutic intracellular activity" refers to a therapeutic activity or function that occurs within a cell and / or involves at least one intracellular species that directly exerts or is directly involved in the activity. Therapeutic activity or function may, for example, involve both extracellular and intracellular species, or, if involved, may optionally be both therapeutic extracellular activity and therapeutic intracellular activity.

[0021]

[0080] The term "inflammatory factor," as the term is recognized in the art, particularly in biomedical science, refers to a factor associated with inflammation. Inflammatory factors may include, but are not limited to, proteins, genes, enzymes, and / or other factors associated with inflammation. The term "enzymatic factor," as the term is recognized in the art, particularly in biomedical science, refers to a factor associated with enzymatic activity, optionally including enzymes associated with inflammation. Inflammatory and / or enzymatic factors may include, but are not limited to, TNFα, iNOS, MMP9, ERK1 / 2, p38, JNK, one or more factors associated with downregulation of pro-inflammatory signaling, one or more factors controlling the expression of one or more genes associated with inflammation, one or more factors controlling the expression of one or more genes associated with apoptosis, one or more factors controlling the expression of MMP9, one or more proteins associated with the MAPK / ERK pathway, one or more enzymes associated with the MAPK / ERK pathway, or any combination thereof. The term "apoptotic factor" refers to a factor associated with cellular apoptosis, as the term is recognized in the art, particularly in biomedical sciences.

[0022]

[0081] The term "wound" refers to an area of ​​a living subject having damaged tissue. The wound may optionally include free radical species, including extracellular free radical species. The wound may optionally include inflammation. The wound may optionally be a wound in skin tissue or optionally include damaged skin tissue. The wound may optionally include the stratum corneum. The wound may optionally include one or more blisters. The wound or damaged tissue therein may optionally include thermally induced damage, chemically induced damage, UV induced damage, mechanical friction damage, infected cellulitis induced damage, and / or radiation induced damage.

[0023]

[0082] The term "free radical species" is intended to be consistent with the term as recognized by those skilled in the art of chemistry or biochemistry. Free radical species are generally molecular species capable of independent existence and containing one or more unpaired electrons. Free radical species may include those that are mutagenic, carcinogenic, cause the production of DNA strand breaks, and / or create DNA-protein crosslinks. Exemplary free radical species include, but are not limited to, reactive oxygen species such as reactive oxygen species (ROS).

[0024]

[0083] The terms "quenching" and "scavenging" are used interchangeably herein and refer to the process of quenching or scavenging free radical species consistent with the technical fields of chemistry or biochemistry. Generally, quenching refers to a process or reaction with or involving a free radical species that results in the conversion / transformation of the free radical species into one or more products that are not free radical species as a result of the reaction, or otherwise cessation of the existence of the free radical species.

[0025]

[0084] The term "non-melanin therapeutic agent" refers to a therapeutic agent that is not a melanin material and does not itself contain melanin material. A therapeutic agent may be, for example, a species such as a compound, molecule, or moiety that is therapeutically or pharmaceutically active when exposed to a living subject, or that can treat or address a condition, such as a disease, in a living subject. For example, a therapeutic agent may be or include a small molecule drug, polymer, peptide, amino acid, DNA, or RNA. Optionally, for example, the therapeutic agent is one or more therapeutic agents (such as one or more compounds, molecules, or moieties) that can promote skin healing.

[0026]

[0085] The term "extracellular" when describing a species or process is intended to be consistent with the technical fields of pharmacology or biochemistry and refers to the described species or process being found or occurring outside of a cell (i.e., not within a cell).

[0027]

[0086] The term "subject" or "patient" refers to a living organism suffering from or having a wound, disease, or condition that can be at least partially treated or corrected by administration of a formulation or melanin material as described herein. Non-limiting examples include humans, other mammals, cows, rats, mice, dogs, monkeys, goats, sheep, cattle, deer, and other non-mammalian animals. In some embodiments, such as some of Aspects 1-61, the subject is a human. In some embodiments, such as some of Aspects 1-61, the subject is a mammal. In some embodiments, such as some of Aspects 1-61, the subject is a mouse. In some embodiments, such as some of Aspects 1-61, the subject is an experimental animal. In some embodiments, such as some of Aspects 1-61, the subject is a rat. In some embodiments, such as some of Aspects 1-61, the subject is a test animal.

[0028]

[0087] The terms "reactive oxygen species" and "ROS," as used interchangeably herein, refer in their ordinary and customary sense to transient species typically formed during exposure to radiation (e.g., UV irradiation) that are capable of inducing oxidative degradation.

[0029]

[0088] The terms "cell" and "biological cell" are used interchangeably and refer to a cell that performs metabolic or other functions sufficient to preserve or replicate its genomic DNA. Cells can be identified by methods well known in the art, including, for example, the presence of an intact membrane, staining with certain dyes, and the ability to produce progeny or, in the case of gametes, the ability to combine with a second gamete to produce viable progeny. Cells may include prokaryotic and eukaryotic cells. Prokaryotic cells include, but are not limited to, bacteria. Eukaryotic cells include, but are not limited to, yeast cells and cells derived from plants and animals, such as mammalian, insect (e.g., Spodoptera), and human cells. A "living cell" is a living, biological cell.

[0030]

[0089] The term "formulation" refers to a melanin (e.g., a melanin derivative) composition that includes melanin or a derivative thereof, a melanin precursor (e.g., a material utilized in the synthesis of melanin), or additional additives such as solvents (e.g., carriers), lubricants, dispersants, oils, fragrances, natural ingredients, pharmaceutically acceptable excipients, and the like.

[0031]

[0090] The term "melanin" generally refers to one or more compounds or materials that function as pigments, for example, when internalized or incorporated into living cells. Note that melanin is not necessarily incorporated into cells. Melanin can be incorporated into or on the cell walls of fungi, for example, to provide rigidity, defense mechanisms, and more. In another illustrative example, melanin is used by birds, such as when melanin is organized into a matrix of keratin or similar types of biomaterial, where it can be organized into monolayers or multilayers to provide structural color, warmth, and more. A melanin compound or material can be, for example, but is not limited to, melanin monomers, melanin oligomers, melanin polymers, melanin nanoparticles, melanin layers (e.g., melanin films or coatings), or other melanin materials. For example, melanin nanoparticles internalized into living cells function as pigments within the cells.

[0032]

[0091] The terms "artificial melanin" and "synthetic melanin" are used interchangeably herein and refer to one or more melanin compounds, molecules, or materials, such as melanin monomers, melanin oligomers, or melanin nanoparticles, that are synthetic and are not derived, at least in part, or preferably entirely, from or extracted from a natural source, such as a biological source, a living organism, or a once-living organism. The terms "synthetic" and "artificial" are used interchangeably herein when referring to melanin or a material containing melanin. The terms "synthetic melanin nanoparticles" and "artificial melanin nanoparticles" are used interchangeably herein and are intended to have the same meaning throughout this disclosure and refer to nanoparticles formed from artificial melanin, such as artificial melanin monomers and / or artificial melanin oligomers. The terms "synthetic melanin film" and "artificial melanin film" are used interchangeably herein and are intended to have the same meaning throughout this disclosure and refer to films formed from artificial melanin, such as artificial melanin monomers and / or artificial melanin oligomers. The terms "synthetic melanin layer" and "artificial melanin layer" are used interchangeably herein and are intended to have the same meaning throughout this disclosure, and refer to a layer formed of artificial melanin, such as artificial melanin monomer and / or artificial melanin oligomer. Artificial melanin nanoparticles, artificial melanin thin films, artificial melanin layers, and any compounds, materials, or preparations comprising any of these, include artificial melanin monomer, artificial melanin oligomer, and / or artificial melanin polymer. Optionally, artificial melanin nanoparticles, artificial melanin thin films, artificial melanin layers, and any compounds, materials, or preparations comprising any of these, consist of or consist essentially of artificial melanin, such as artificial melanin monomer, artificial melanin oligomer, and / or artificial melanin polymer. Optionally, artificial melanin nanoparticles, artificial melanin thin films, artificial melanin layers, and any compounds, materials, or preparations comprising any of these, are free (or substantially free) of artificial melanin monomer, but include artificial melanin oligomer and / or artificial melanin polymer.Preferably, each artificial melanin monomer, artificial melanin oligomer, and artificial melanin polymer of the artificial melanin nanoparticles, artificial melanin thin films, artificial melanin layers, and any compound, material, or formulation comprising any of these, is not bound to, conjugated to, attached to, coated by, enclosed by, or otherwise chemically associated with a natural or biological proteinaceous lipid. A natural or biological proteinaceous lipid refers to a lipid that is naturally occurring or biologically derived or extracted from a natural or biological source, such as a once-living organism, and the lipid contains one or more proteins, such as the lipid (plasma) membrane of a melanocyte or melanosome. Optionally, each artificial melanin monomer, artificial melanin oligomer, and artificial melanin polymer of the artificial melanin nanoparticles, artificial melanin films, artificial melanin layers, and any compound, material, or formulation comprising any of these, is not bound to, conjugated to, attached to, coated by, enclosed by, or otherwise chemically associated with a natural or biological lipid (e.g., a lipid bilayer, lipid membrane, or phospholipid compound). Natural or biological lipid refers to a lipid derived from nature or a biological source, such as a lipid derived from a previously living organism. Optionally, each artificial melanin monomer, artificial melanin oligomer, and artificial melanin polymer of the artificial melanin nanoparticles, artificial melanin films, artificial melanin layers, and any compound, material, or formulation comprising any of these, is bound to, conjugated to, attached to, coated by, enclosed by, and / or otherwise associated with a synthetic or artificial lipid or a synthetic or artificial phospholipid. Synthetic or artificial lipids refer to lipids that are synthesized and not derived or extracted from natural or biological sources, such as former living organisms.

[0033]

[0092] As used herein, modification and functionalization may be used interchangeably to refer to modifying or functionalizing artificial melanin nanoparticles with a modifying agent to change one or more properties of the artificial melanin nanoparticles, such as increasing hydrophobicity.

[0034]

[0093] The term "artificial melanin precursor" refers to a compound or material that can form an artificial melanin material after chemical reaction, such as after chemical reaction with an oxidizing agent. An artificial melanin precursor may be, but is not necessarily, a melanin itself. For example, an artificial melanin precursor may be, but is not necessarily, a melanin monomer. For example, contacting an artificial melanin precursor, such as a melanin monomer, with an oxidizing agent can result in oxidative oligomerization (or polymerization) between the artificial melanin precursors, thereby forming one or more artificial melanin materials.

[0035]

[0094] The term "selenomelanin" refers to a melanin that includes selenium. For example, a selenomelanin material includes selenium. Preferably, the chemical formula of the selenomelanin material includes selenium (e.g., at least one selenium atom).

[0036]

[0095] In certain embodiments, the term "pheomelanin" refers to a melanin whose chemical formula includes at least one substituted or unsubstituted benzothiazine, at least one substituted or unsubstituted benzothiazole, at least one substituted or unsubstituted benzoselenazole, at least one substituted or unsubstituted benzoselenazine, at least one derivative of any of these, or any combination thereof. In certain embodiments, the term pheomelanin refers to a melanin made from L-DOPA and cysteine ​​whose chemical formula includes at least one substituted or unsubstituted benzothiazine, at least one substituted or unsubstituted benzothiazole, at least one substituted or unsubstituted benzoselenazole, at least one substituted or unsubstituted benzoselenazine, at least one derivative of any of these, or any combination thereof. In certain embodiments, selenium pheomelanin refers to a melanin whose chemical formula includes at least one substituted or unsubstituted benzoselenazole, at least one substituted or unsubstituted benzoselenazine, at least one derivative of any of these, or any combination thereof.

[0037]

[0096] In certain embodiments, the term eumelanin refers to a melanin whose chemical formula includes at least one dihydroxyindole (DHI) (e.g., 5,6-dihydroxyindole), at least one dihydroxyindole-2-carboxylic acid (DHICA) (e.g., 5,6-dihydroxyindole-2-carboxylic acid), or a combination thereof.

[0038]

[0097] As used herein, the term "nanoparticle" refers to a physical particle having at least one size characteristic or physical dimension less than 1 μm. Preferably, as used herein, the term "nanoparticle" refers to a physical particle whose longest size characteristic or physical dimension is less than 1 μm.

[0039]

[0098] The term "size characteristic" refers to a property or set of properties of a particle that is directly or indirectly related to a size attribute. According to some embodiments, the size characteristic corresponds to an empirically derived size characteristic of the detected particle(s), such as a size characteristic based on, determined by, or corresponding to data from any technique or device that can be used to determine particle size, such as electron microscopy (e.g., SEM and TEM) or light scattering (e.g., DLS). For example, the size characteristic may correspond to spherical particles that exhibit similar or substantially the same properties, such as aerodynamic, hydrodynamic, optical, and / or electrical properties, when the particle(s) are detected. According to some embodiments, the size characteristic corresponds to a physical dimension, such as cross-sectional size (e.g., length, width, thickness, or diameter).

[0040]

[0099] The term "particle" refers to small solid objects that can be dispersed and / or suspended in a fluid (e.g., a liquid). For example, a slurry, a dispersion, and a suspension each contain particles in a fluid. The terms "particle" and "particulate" are sometimes used interchangeably. An exemplary particle is an artificial melanin nanoparticle. Multiple particles may associate with each other to form particle agglomerates. Generally, the term "particle," such as "nanoparticle" or "melanin nanoparticle," refers to individual particles rather than agglomerates of such individual particles.

[0041]

[0100] The term "dispersed" refers to species, such as particles, in a fluid that form a dispersion. As used herein, the term "dispersion" broadly refers to a mixture of one or more chemical species, such as particles, in a fluid, as in the art-recognized meanings of solution, dispersion, and / or suspension. Chemical species, such as particles, dispersed in a dispersion may be referred to as dispersed species. Preferably, a dispersion is a mixture of particles, such as artificial melanin particles, in a liquid, such as a solvent. Preferably, but not necessarily, a dispersion is a homogeneous mixture. In the context of a dispersion, the term "homogeneous" refers to a liquid mixture that appears uniform to the naked eye. In contrast, a heterogeneous liquid mixture contains particles that have settled from or are suspended in the liquid mixture and are large enough to be clearly visible in the liquid mixture with the naked eye. A heterogeneous liquid mixture includes, for example, settled and / or sedimented particles. Preferably, but not necessarily, the term "dispersion" is intended broadly to include dispersions, such as solutions and colloids, that are not heterogeneous liquid mixtures. Preferably, but not necessarily, a dispersion is a microscopically homogeneous or uniform mixture of particles in a liquid such as a solvent. Preferably, but not necessarily, a dispersion is thermodynamically favorable to remain stably dispersed, or thermodynamically favorable to separate by sedimentation, but sedimentation is kinetically slowed or prevented. Particles of a dispersion characterized as stably dispersed remain dispersed in the dispersion and do not settle or precipitate from the liquid of the dispersion under ambient temperature and pressure (NTP) and air exposure for at least 5 hours, preferably at least 12 hours, preferably at least 24 hours, more preferably at least 1 week. In embodiments, particles that are not dispersed or cannot be dispersed in a fluid refer to particles that form sediment or precipitate when mixed in a fluid.

[0042]

[0101] When referring to a material, such as a polymer, that is aqueous, the term "aqueous" refers to the material being dispersed, dissolved, or otherwise solvated by water. An "aqueous solution" refers to a solution containing water as the solvent and one or more solute species that are dispersed, dissolved, or otherwise solvated by water. An aqueous process, such as polymerization, is a process that occurs in an aqueous solution. Optionally, but not necessarily, the aqueous solution or aqueous solvent contains no more than 20 vol.%, optionally no more than 15 vol.%, optionally no more than 10 vol.%, and preferably no more than 5 vol.% of non-aqueous or organic species. Optionally, but not necessarily, the aqueous solution or aqueous solvent contains no more than 20 vol.%, optionally no more than 15 vol.%, optionally no more than 10 vol.%, and preferably no more than 5 vol.% of non-aqueous liquids.

[0043]

[0102] The term "aging," as used herein with respect to artificial melanin nanoparticles, refers to the process by which synthesized and isolated artificial melanin nanoparticles oxidize over time during exposure to oxygen, such as that resulting from air exposure, and optionally become even darker. Isolated artificial melanin nanoparticles can be artificial melanin nanoparticles that have been purified, such as by centrifugation, and redispersed in water, such as ultrapure water, or optionally in another solvent or solvent solution. For example, artificial melanin nanoparticles can age if the particles are dispersed in water and stored in a capped (closed) vial for an extended period of time without being opened, due to residual oxygen remaining in the container. The aging process can alter certain properties or characteristics of the artificial melanin nanoparticles, such as increasing their solubility in organic solvents or decreasing their toxicity to certain living biological cells. For example, without wishing to be bound by any particular theory, in some embodiments, newly synthesized artificial melanin nanoparticles can be dynamic, allowing monomers or oligomers to enter cells when internalized by cells. For example, without wishing to be bound by any particular theory, in some embodiments, newly synthesized artificial melanin nanoparticles may be dynamic and may have a surface chemical oxidation state that is not optimal for viable cells when internalized by cells. For example, without wishing to be bound by any particular theory, in some embodiments, the aging process may lead to more cross-linking or other forms of chemical association between the melanin compounds (monomers, oligomers) in the artificial melanin nanoparticles, potentially leading to reduced influx of the melanin compounds into cells and / or reduced cytotoxicity, such as by altering or stabilizing the surface chemistry of the particles.

[0044]

[0103] The term "peak size" refers to the statistical mode, or peak frequency, of a particle size distribution, or the particle size most commonly found in the particle size distribution. Particle size distributions can be measured, for example, using dynamic light scattering.

[0045]

[0104] The term "substantially" refers to a property, condition, or value that is within 20%, 10%, 5%, 1%, optionally within 0.1%, or equivalent to a reference property, condition, or value. The terms "substantially equal," "substantially equivalent," or "substantially unchanged," when used in conjunction with a reference value describing a property or condition, refer to a value that is within 20%, 10%, optionally within 5%, optionally within 1%, optionally within 0.1%, or optionally equivalent to the described reference value. For example, a diameter is substantially equal to 100 nm (or "is substantially 100 nm") if the diameter value is within 20%, optionally within 10%, optionally within 5%, optionally within 1%, 0.1%, or optionally equal to 100 nm. The term "substantially greater than," when used in conjunction with a reference value describing a property or condition, refers to a value that is at least 1%, optionally at least 5%, optionally at least 10%, or optionally at least 20% greater than the reference value described. The term "substantially less than," when used in conjunction with a reference value describing a property or condition, refers to a value that is at least 1%, optionally at least 5%, optionally at least 10%, or optionally at least 20% less than the reference value described.

[0046]

[0105] As used herein, the term "about" refers to a range of values ​​that includes the specified value that one of ordinary skill in the art would consider to be fairly close to the specified value. In embodiments, about refers to within a standard deviation using measurements generally accepted in the art. In embodiments, about refers to a range that extends to + / - 10% of the specified value. In embodiments, about refers to the specified value.

[0047]

[0106] As used herein, the term "administering" refers to oral administration, administration as an inhaled aerosol or inhaled dry powder, suppository, topical contact, intravenous, parenteral, intraperitoneal, intramuscular, intralesional, intrathecal, intranasal, or subcutaneous administration to a subject, or implantation of a sustained-release device, e.g., a mini-osmotic pump. Administration can be by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration can include, for example, intravenous, intramuscular, intraarteriolar, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, and the like. By "co-administering," it is meant that the compositions described herein are administered simultaneously with, immediately before, or immediately after the administration of one or more additional therapies, e.g., cancer therapies such as chemotherapy, hormonal therapy, radiation therapy, or immunotherapy. The compounds of the present invention can be administered alone or co-administered to a patient. Co-administration is intended to include simultaneous or sequential administration of compounds (more than one compound or agent) individually or in combination. The compositions of the present invention can be delivered topically or transdermally and can be formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, liniments, powders, and aerosols. Oral preparations include tablets, pills, powders, dragees, capsules, liquids, lozenges, cachets, gels, syrups, slurries, suspensions, etc., suitable for ingestion by the patient. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. Liquid form preparations include solutions, suspensions, and emulsions, e.g., water or water / propylene glycol solutions. The compositions of the present invention may additionally contain components to provide sustained release and / or comfort. Such components include high molecular weight anionic mucomimetic polymers, gelling polysaccharides, and micronized drug carrier substrates. These components are discussed in more detail in U.S. Patent Nos. 4,911,920, 5,403,841, 5,212,162, and 4,861,760, the entire contents of which are incorporated herein by reference in their entirety for all purposes.The compositions of the present invention can also be delivered as microspheres for sustained release in the body. For example, microspheres can be administered via intradermal injection of drug-containing microspheres for slow subcutaneous release (see Rao, J. Biomater Sci. Polym. Ed. 7:623-645, 1995), as biodegradable, injectable gel formulations (see, e.g., Gao Pharm. Res. 12:857-863, 1995), or as microspheres for oral administration (see, e.g., Eyles, J. Pharm. Pharmacol. 49:669-674, 1997). In another embodiment, formulations of the compositions of the present invention can be delivered through the use of liposomes that fuse with or are endocytosed by cell membranes, i.e., through the use of receptor ligands attached to the liposomes that bind to surface membrane protein receptors of the cells, resulting in endocytosis. Liposomes can be used to deliver drugs to target cells, particularly when the liposome surface bears receptor ligands specific to the target cells or is otherwise preferentially directed to a particular organ. Delivery of the compositions of the invention into target cells in vivo can be focused (see, e.g., Al-Muhammed, J. Microencapsul. 13:293-306, 1996; Chonn, Curr. Opin. Biotechnol. 6:698-708, 1995; Qstio, Am. J. Hasp. Pharm. 46:1576-1587, 1989).

[0048]

[0107] The term "contacting" may include reacting, interacting, or physically touching two species, where the two species may be, for example, a pharmaceutical composition as described herein and a cell. In embodiments, contacting includes, for example, interacting a pharmaceutical composition as described herein with a cell or a patient.

[0049]

[0108] The terms "analog" and "analogue" are used interchangeably and according to their obvious ordinary meaning within chemistry and biology to refer to a chemical compound that is structurally similar to another compound (i.e., a so-called "reference" compound) but differs in composition, e.g., the replacement of an atom by an atom of a different element, or the presence of a particular functional group, or the replacement of a functional group by another functional group, or the absolute stereochemistry of one or more chiral centers of the reference compound, including isomers thereof. Thus, an analog is a compound that is similar or equivalent in function and appearance to the reference compound, but not similar or equivalent in structure or origin.

[0050]

[0109] Unless otherwise specified, the term "molecular weight" refers to average molecular weight. Unless otherwise specified, the term "average molecular weight" refers to number average molecular weight. Number average molecular weight is defined as the total weight of a sample volume divided by the number of molecules in the sample. As is customary and well known in the art, peak average molecular weight and weight average molecular weight may be used to characterize the molecular weight of a distribution of polymers within a sample.

[0051]

[0110] The term "weight average molecular weight" (M w ) is the molecular weight of each polymer molecule (M i ) to its weight fraction (w i ) multiplied by: M w =Σw i M i As is customary and well known in the art, peak average molecular weight and number average molecular weight may be used to characterize the molecular weight of a distribution of polymers within a sample.

[0052]

[0111] The term "wt.%" or "wt%" refers to weight percent or mass fraction expressed as mass percentage. The term "at.%" or "at%" refers to atomic percentage or atomic ratio expressed as the percentage of one type of atom relative to all atoms in a given substance such as a molecule, compound, material, nanoparticle, polymer, dispersion, etc.

[0053]

[0112] The term "oligomerization" refers to a chemical process that converts a monomer or mixture of monomers into an oligomer. The term "oxidative oligomerization" refers to a chemical process of oligomerization that involves the chemical oxidation of one or more monomers to form an oligomer. Oligomerization is a polymerization process in which oligomers are formed as a result of polymerization.

[0054]

[0113] As used herein, the term "polymer" refers to a molecule composed of repeating structural units, also called base units, connected by covalent chemical bonds, often characterized by several repeating units (e.g., two or more base units). As used herein, the term "polymer" includes "oligomer" (i.e., an oligomer is a polymer; i.e., a polymer is optionally an oligomer). "Oligomer" refers to a molecule composed of repeating structural units, also called base units, connected by covalent chemical bonds, often characterized by fewer repeating units, such that an oligomer is a low-molecular-weight polymer. Preferably, but not necessarily, for example, an oligomer has 100 or fewer repeating units. Preferably, but not necessarily, for example, an oligomer has a lower molecular weight, such as 10,000 Da or less. An oligomer may be the polymerization product of one or more monomer precursors. The polymerization of one or more monomers or monomer precursors resulting in the formation of an oligomer may be referred to as oligomerization. Oligomers optionally contain 100 or fewer, 50 or fewer, 15 or fewer, 12 or fewer, 10 or fewer, or 5 or fewer repeating units (or "basic units"). Oligomers can be characterized as having a molecular weight of 10,000 Da or fewer, 5,000 Da or fewer, 1,000 Da or fewer, 500 Da or fewer, or 200 Da or fewer. Dimers, trimers, tetramers, or pentamers are oligomers having two, three, four, or five repeating units or basic units, respectively. Polymers can have, for example, more than 100 repeating units. Polymers can have high molecular weights, such as, for example, more than 10,000 Da, and in some embodiments, 50,000 Da or more or 100,000 Da or more. The term polymer includes homopolymers, or polymers consisting essentially of a single repeating monomer subunit. The term polymer also includes copolymers, which are formed when two or more different types of monomers are linked within the same polymer. Copolymers may contain two or more types of monomer subunits, including random, block, brush, brush-block, alternating, segmented, grafted, tapered, and other structures.Useful polymers include organic or inorganic polymers that may be in an amorphous, semi-amorphous, crystalline, or semi-crystalline state. Polymer side chains that can crosslink (e.g., physically crosslink) the polymer can be useful in some applications.

[0055]

[0114] "Oligomer" refers to a molecule composed of repeating structural units, also called basic units, connected by covalent chemical bonds, often characterized by fewer repeating units than those of a polymer (e.g., 100 or fewer repeating units) and a lower molecular weight than a polymer (e.g., 10,000 Da or less). An oligomer may be the polymerization product of one or more monomer precursors. The polymerization of one or more monomers or monomer precursors resulting in the formation of an oligomer is sometimes referred to as oligomerization. An oligomer optionally contains 100 or fewer, 50 or fewer, 15 or fewer, 12 or fewer, 10 or fewer, or 5 or fewer repeating units (or "basic units"). An oligomer may be characterized as having a molecular weight of 10,000 Da or less, 5,000 Da or less, 1,000 Da or less, 500 Da or less, or 200 Da or less. A dimer, trimer, tetramer, or pentamer is an oligomer having two, three, four, or five repeating units, or base units, respectively.

[0056]

[0115] As used herein, the term "group" may refer to a functional group of a chemical compound. A group of the compound refers to an atom or collection of atoms that is part of the compound. Groups of the present invention may be attached to other atoms of the compound via one or more covalent bonds. Groups may also be characterized in terms of their valence state. The present invention includes groups characterized as monovalent, divalent, trivalent, etc.

[0057]

[0116] The term "moiety" refers to a group, such as a functional group, of a chemical compound or molecule. A moiety is a collection of atoms that is part of a chemical compound or molecule. The present invention includes moieties characterized by a valence state, such as monovalent, divalent, trivalent, etc. Generally, although not necessarily, a moiety contains more than one functional group.

[0058]

[0117] As used herein, the term "substituted" refers to a compound in which one or more hydrogens have been replaced by another functional group, provided that the normal valence of the designated atom is not exceeded. Exemplary substituents include, but are not limited to, halogen or halide, alkyl, cycloalkyl, aryl, heteroaryl, acyl, alkoxy, alkenyl, alkynyl, alkylaryl, arylene, heteroarylene, alkenylene, cycloalkenylene, alkynylene, hydroxyl (—OH), carbonyl (RCOR′), sulfide (e.g., RSR′), phosphate (ROP(═O)(OH)), azo (RNNR′), cyanate (ROCN), amine (e.g., primary, secondary, or tertiary), imine (RC(═NH)R′), nitrile (RCN), pyridinyl (or pyridyl), diamine, triamine, azide, diimine, triimine, amide, diimide, or ether (ROR′) (wherein each of R and R′ is independently hydrogen or a substituted or unsubstituted alkyl group, aryl group, alkenyl group, or combination thereof). Optionally substituted functional groups are also described below. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the term substituted refers to a compound in which each of more than one hydrogen is replaced with another functional group, such as a halogen group. For example, when a substituent is oxo (i.e., ═O), two hydrogens on the atom are replaced. The substituent can be any substituent described herein. For example, the substituent can include one or more of hydroxyl, amino (e.g., primary, secondary, or tertiary), aldehyde, carboxylic acid, ester, amide, ketone, nitro, urea, guanidine, cyano, fluoroalkyl (e.g., trifluoromethane), halo (e.g., fluoro), aryl (e.g., phenyl), heterocyclyl or heterocyclic group (i.e., a cyclic group, e.g., aromatic (e.g., heteroaryl) or non-aromatic, having one or more heteroatoms), oxo, or combinations thereof. Combinations of substituents and / or variables are permissible provided that the substitution does not significantly adversely affect the synthesis or use of the compound.

[0059]

[0118] As used herein, the term "derivative" refers to any of a group consisting of hydrogen, halogen or halide, alkyl, cycloalkyl, aryl, heteroaryl, acyl, alkoxy, alkenyl, alkynyl, alkylaryl, arylene, heteroarylene, alkenylene, cycloalkenylene, alkynylene, hydroxyl (-OH), carbonyl (RCOR'), sulfide (e.g., RSR'), phosphate (ROP(=O)(OH)2), azo (RNNR'), cyanate (ROCN), amine (e.g., primary, secondary, or tertiary), imine (RC(=NH)R'), nitrile (RCN), pyridinyl (or pyridyl), diamine, triamine, azide, diimine, triimine, amide, diimide, or ether (ROR') (wherein each of R and R' is independently hydrogen or a substituted or unsubstituted alkyl group, aryl group, alkenyl group, or combination thereof). Optional substituted functional groups are also described below. Preferably, the term "derivative" refers to a compound in which one or two atoms or functional groups are independently replaced by another atom or functional group. Optionally, the term derivative does not refer to or include the replacement of a chalcogen atom (S, Se) that is a member of a heterocyclic group. Optionally, unless otherwise stated, the term derivative does not refer to or include replacement of a chalcogen atom (S, Se) or N (nitrogen) when the chalcogen atom and N are members of the same heterocyclic group. Optionally, but not necessarily, the term derivative does not include disruption of the ring structure, replacement of a ring member, or removal of a ring member.

[0060]

[0119] As is customary and well known in the art, hydrogen atoms in formulae are not always explicitly shown, e.g., hydrogen atoms bonded to carbon atoms of aromatic, heteroaromatic, and alicyclic rings are not always explicitly shown. The structures depicted herein, e.g., in the context of the formulae and the illustrations of the structures in the figures and drawings, are intended to convey to those of ordinary skill in the art the chemical makeup of the compounds of the methods and compositions of the invention, and as would be understood by one of ordinary skill in the art, the depicted structures do not depict the specific positions and / or orientations of the atoms and corresponding bond angles between the atoms of these compounds.

[0061]

[0120] The term "hydrocarbyl group" refers to any univalent radical or group derived from a hydrocarbon, or in other words, a univalent group formed by removing a hydrogen atom from a hydrocarbon. Examples of hydrocarbyl groups include, but are not limited to, methyl, ethyl, phenyl, and the like. Hydrocarbyl groups can be substituted (see also the definition of substituents above), such as hydrogen replaced by a halogen, or can be unsubstituted. Hydrocarbyl groups can be saturated or unsaturated.

[0062]

[0121] As used herein, the terms "alkylene" and "alkylene group" are used interchangeably and refer to a divalent radical derived from an alkyl group, as defined herein. The present invention includes compounds having one or more alkylene groups. The alkylene groups of some compounds function as linker groups and / or spacers. The compounds of the present invention may also include compounds having one or more linker groups (e.g., L 1 ~L 6 ) as, for example, substituted and / or unsubstituted C1-C 20 Alkylene, C1-C 10 It may contain alkylene and C1 to C5 alkylene groups.

[0063]

[0122] As used herein, the terms "cycloalkylene" and "cycloalkylene group" are used interchangeably and refer to a divalent radical derived from a cycloalkyl group, as defined herein. The present invention includes compounds having one or more cycloalkylene groups. The cycloalkyl groups of some compounds function as linking and / or spacer groups. The compounds of the present invention may also contain one or more linker groups (e.g., L 1 ~L 6 ) as, for example, substituted and / or unsubstituted C3-C 20 Cycloalkylene, C3-C 10 It may contain cycloalkylene and C3 to C5 cycloalkylene groups.

[0064]

[0123] As used herein, the terms "arylene" and "arylene group" are used interchangeably and refer to a divalent radical derived from an aryl group, as defined herein. The present invention includes compounds having one or more arylene groups. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, an arylene is a divalent radical derived from an aryl group by removal of hydrogen atoms from two endocyclic carbon atoms of the aromatic ring of the aryl group. The arylene groups of some compounds function as linking and / or spacer groups. The arylene groups of some compounds function as chromophores, fluorophores, aromatic antennae, dyes, and / or imaging groups. The compounds of the present invention may also include one or more linker groups (e.g., L 1 ~L 6 ) as, for example, substituted and / or unsubstituted C3-C 30 Arylene, C3-C 20 Arylene, C3-C 10 Includes arylene and C1-C5 arylene groups.

[0065]

[0124] As used herein, the terms "heteroarylene" and "heteroarylene group" are used interchangeably and refer to a divalent radical derived from a heteroaryl group, as defined herein. The present invention includes compounds having one or more heteroarylene groups. In certain embodiments, a heteroarylene is a divalent radical derived from a heteroaryl group by removal of hydrogen atoms from two endocyclic carbon or nitrogen atoms of the heteroaromatic or aromatic ring of the heteroaryl group. The heteroarylene groups of some compounds function as linking and / or spacer groups. The heteroarylene groups of some compounds function as chromophores, aromatic antennae, fluorophores, dyes, and / or imaging groups. The compounds of the present invention may also include one or more linker groups (e.g., L 1 ~L 6 ) as, for example, substituted and / or unsubstituted C3-C 30 Heteroarylene, C3-C 20 Heteroarylene, C1-C 10 Includes heteroarylene and C3-C5 heteroarylene groups.

[0066]

[0125] As used herein, the terms "alkenylene" and "alkenylene group" are used interchangeably and refer to a divalent radical derived from an alkenyl group, as defined herein. The present invention includes compounds having one or more alkenylene groups. The alkenylene groups of some compounds function as linking and / or spacer groups. The compounds of the present invention may also include one or more linker groups (e.g., L 1 ~L 6 ) as, for example, substituted and / or unsubstituted C2-C 20 Alkenylene, C2-C 10 Includes alkenylene and C2-C5 alkenylene groups.

[0067]

[0126] As used herein, the terms "cycloalkenylene" and "cycloalkenylene group" are used interchangeably and refer to a divalent radical derived from a cycloalkenyl group, as defined herein. The present invention includes compounds having one or more cycloalkenylene groups. The cycloalkenylene groups of some compounds function as linking and / or spacer groups. The compounds of the present invention may also include one or more linker groups (e.g., L 1 ~L 6 ) as, for example, substituted and / or unsubstituted C3-C 20 Cycloalkenylene, C3-C 10 Includes cycloalkenylene and C3-C5 cycloalkenylene groups.

[0068]

[0127] As used herein, the terms "alkynylene" and "alkynylene group" are used interchangeably and refer to a divalent radical derived from an alkynyl group, as defined herein. The present invention includes compounds having one or more alkynylene groups. The alkynylene groups of some compounds function as linking and / or spacer groups. The compounds of the present invention may also include one or more linker groups (e.g., L 1 ~L 6 ) as, for example, substituted and / or unsubstituted C2-C 20 Alkynylene, C2-C 10 Includes alkynylene and C2-C5 alkynylene groups.

[0069]

[0128] As used herein, the term "halo" refers to a halogen radical such as fluoro (-F), chloro (-Cl), bromo (-Br), iodo (-I) or astato (-At).

[0070]

[0129] The term "heterocyclic" refers to a ring structure containing at least one other type of atom in addition to carbon within the ring. Examples of such heteroatoms include nitrogen, oxygen, and sulfur. Heterocyclic rings include heteroalicyclic rings and heteroaromatic rings. Examples of heterocyclic rings include, but are not limited to, pyrrolidinyl, piperidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, furyl, thienyl, pyridyl, quinolyl, isoquinolyl, pyridazinyl, pyrazinyl, indolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, pyridinyl, benzoxadiazolyl, benzothiadiazolyl, triazolyl, and tetrazolyl groups. The atoms of the heterocyclic ring can be bonded to a wide variety of other atoms and functional groups, for example, other atoms and functional groups provided as substituents.

[0071]

[0130] The term "carbocyclic" refers to a ring structure containing only carbon atoms in the ring. The carbon atoms of a carbocyclic ring can be bonded to a wide range of other atoms and functional groups, including other atoms and functional groups provided as substituents.

[0072]

[0131] The term "alicyclic ring" refers to a ring or multiple fused rings that is not aromatic. Alicyclic rings include both carbocyclic and heterocyclic rings.

[0073]

[0132] The term "aromatic ring" refers to a ring or multiple fused rings containing at least one aromatic ring group. The term aromatic ring includes aromatic rings containing carbon, hydrogen, and heteroatoms. Aromatic rings include carbocyclic and heterocyclic aromatic rings. Aromatic rings are components of aryl groups.

[0074]

[0133] The term "fused ring" or "fused ring structure" refers to multiple alicyclic and / or aromatic rings provided in a fused ring configuration, such as fused rings that share at least two ring carbon atoms and / or heteroatoms.

[0075]

[0134] As used herein, the term "alkoxyalkyl" refers to a substituent of the formula alkyl-O-alkyl.

[0076]

[0135] As used herein, the term "polyhydroxyalkyl" refers to a substituent having 2 to 12 carbon atoms and 2 to 5 hydroxyl groups, such as a 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl, or 2,3,4,5-tetrahydroxypentyl residue.

[0077]

[0136] As used herein, the term "polyalkoxyalkyl" refers to a group of alkyl-(alkoxy) n -alkoxy, where n is an integer from 1 to 10, preferably 1 to 4, and more preferably 1 to 3 for some embodiments.

[0078]

[0137] Amino acids include glycine, alanine, valine, leucine, isoleucine, methionine, proline, phenylalanine, tryptophan, asparagine, glutamine, glycine, serine, threonine, serine, threonine, asparagine, glutamine, tyrosine, cysteine, lysine, arginine, histidine, aspartic acid, and glutamic acid. As used herein, reference to "side chain residues of natural α-amino acids" specifically includes the side chains of the amino acids referenced above. Peptides and peptide moieties, as used and described herein, comprise two or more amino acid groups joined via a peptide bond.

[0079]

[0138] Amino acids and amino acid groups refer to naturally occurring amino acids, non-naturally occurring (non-naturally occurring) amino acids, and / or combinations thereof. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphorylated serine. Naturally occurring α-amino acids include, but are not limited to, alanine (Ala), cysteine ​​(Cys), aspartic acid (Asp), glutamic acid (Glu), phenylalanine (Phe), glycine (Gly), histidine (His), isoleucine (Ile), arginine (Arg), lysine (Lys), leucine (Leu), methionine (Met), asparagine (Asn), proline (Pro), glutamine (Gln), serine (Ser), threonine (Thr), valine (Val), tryptophan (Trp), tyrosine (Tyr), and combinations thereof. Naturally occurring stereoisomers of α-amino acids include, but are not limited to, D-alanine (D-Ala), D-cysteine ​​(D-Cys), D-aspartic acid (D-Asp), D-glutamic acid (D-Glu), D-phenylalanine (D-Phe), D-histidine (D-His), D-isoleucine (D-Ile), D-arginine (D-Arg), D-lysine (D-Lys), D-leucine (D-Leu), D-methionine (D-Met), D-asparagine (D-Asn), D-proline (D-Pro), D-glutamine (D-Gln), D-serine (D-Ser), D-threonine (D-Thr), D-valine (D-Val), D-tryptophan (D-Trp), D-tyrosine (D-Tyr), and combinations thereof.

[0080]

[0139] Non-naturally occurring (non-naturally occurring) amino acids include, but are not limited to, amino acid analogs in either the L- or D-configuration, amino acid mimetics, synthetic amino acids, N-substituted glycines, and N-methyl amino acids that function in a manner similar to naturally occurring amino acids. For example, an "amino acid analog" can be a non-naturally occurring amino acid that has the same basic chemical structure (i.e., a hydrogen, a carboxyl group, and a carbon bonded to an amino group) as a naturally occurring amino acid, but has a modified side group or a modified peptide backbone, such as homoserine, norleucine, methionine sulfoxide, or methionine methylsulfonium. An "amino acid mimetic" refers to a chemical compound that has a structure that differs from the general chemical structure of an amino acid, but functions in a manner similar to a naturally occurring amino acid. Amino acids may be referred to herein by either their commonly known three-letter symbols or the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission.

[0081]

[0140] The terms "monomer unit," "repeating monomer unit," "repeat unit," and "polymerized monomer" may be used interchangeably and refer to a monomeric portion of a polymer described herein that is derived from or is the product of polymerization of one individual "monomer" or "polymerizable monomer." Each individual monomer unit of a polymer is derived from or is the product of polymerization of one polymerizable monomer. Each individual "monomer unit" or "repeat unit" of a polymer comprises one (polymerized) polymer backbone group. For example, in a polymer comprising monomer units X and Y arranged as XYXYXYXY (where each X is identical to each X and each Y is identical to each Y), each X and each Y may be independently referred to as a repeat unit or monomer unit.

[0082]

[0141] Alkyl groups include straight-chain, branched, and cyclic alkyl groups. Alkyl groups include those having 1 to 30 carbon atoms. Alkyl groups include small alkyl groups having 1 to 3 carbon atoms. Alkyl groups include medium-length alkyl groups having 4 to 10 carbon atoms. Alkyl groups include long alkyl groups having more than 10 carbon atoms, particularly those having 10 to 30 carbon atoms. The term cycloalkyl specifically refers to alkyl groups having ring structures such as those having 3 to 30 carbon atoms, optionally 3 to 20 carbon atoms, and optionally 2 to 10 carbon atoms, including alkyl groups having one or more rings. Cycloalkyl groups include those having one or more 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered carbocyclic ring(s), particularly those having one or more 3-, 4-, 5-, 6-, 7-, or 8-membered ring(s). The carbocyclic ring within the cycloalkyl group can also carry an alkyl group. Cycloalkyl groups can include bicyclic and tricyclic alkyl groups. The alkyl group is optionally substituted. Substituted alkyl groups include, among others, those substituted with aryl groups, which in turn can be optionally substituted. Particular alkyl groups include methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, s-butyl, t-butyl, cyclobutyl, n-pentyl, branched pentyl, cyclopentyl, n-hexyl, branched hexyl, and cyclohexyl groups, all of which are optionally substituted. Substituted alkyl groups include fully halogenated or semi-halogenated alkyl groups, such as alkyl groups in which one or more hydrogens are replaced with one or more fluorine, chlorine, bromine, and / or iodine atoms. Substituted alkyl groups include fully fluorinated or semi-fluorinated alkyl groups, such as alkyl groups in which one or more hydrogens are replaced with one or more fluorine atoms. Alkoxy groups are alkyl groups modified by oxygen linkage, which can be represented by the formula RO and are sometimes referred to as alkyl ether groups. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, and heptoxy. Alkoxy groups include substituted alkoxy groups in which the alkyl portion of the group is substituted as described herein in connection with the description of alkyl groups.As used herein, MeO- refers to CHO-. Some embodiments of the present invention comprise alkyl groups as terminal groups, such as polymer backbone terminal groups and / or polymer side chain terminal groups. Substituted alkyl groups may include substitutions incorporating one or more silyl groups, e.g., substitutions in which one or more carbons are replaced by Si.

[0083]

[0142] Alkenyl groups include straight-chain, branched, and cyclic alkenyl groups. Alkenyl groups include those having one, two, or more double bonds, and those in which two or more of the double bonds are conjugated. Alkenyl groups include those having 2 to 20 carbon atoms. Alkenyl groups include small alkenyl groups having 2 to 3 carbon atoms. Alkenyl groups include medium-length alkenyl groups having 4 to 10 carbon atoms. Alkenyl groups include long alkenyl groups having more than 10 carbon atoms, particularly those having 10 to 20 carbon atoms. Cycloalkenyl groups include those in which the double bond is within the ring or within an alkenyl group attached to the ring. The term cycloalkenyl specifically refers to alkenyl groups having ring structures, including alkenyl groups having one or more 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered carbon ring(s), particularly those having one or more 3-, 4-, 5-, 6-, or 7-membered ring(s). The carbocyclic rings within a cycloalkenyl group can also carry alkyl groups. Cycloalkenyl groups can include bicyclic and tricyclic alkenyl groups. Alkenyl groups are optionally substituted. Substituted alkenyl groups include, among others, those substituted with alkyl or aryl groups, which in turn can be optionally substituted. Particular alkenyl groups include ethenyl, prop-1-enyl, prop-2-enyl, cycloprop-1-enyl, but-1-enyl, but-2-enyl, cyclobut-1-enyl, cyclobut-2-enyl, pent-1-enyl, pent-2-enyl, branched pentenyl, cyclopent-1-enyl, hex-1-enyl, branched hexenyl, and cyclohexenyl, all of which are optionally substituted. Substituted alkenyl groups include fully halogenated or semi-halogenated alkenyl groups, such as alkenyl groups in which one or more hydrogen atoms have been replaced with one or more fluorine, chlorine, bromine, and / or iodine atoms. Substituted alkenyl groups include fully fluorinated or semi-fluorinated alkenyl groups, such as alkenyl groups in which one or more hydrogen atoms have been replaced with one or more fluorine atoms. The compositions of some embodiments of the present invention comprise alkenyl groups as end groups, such as polymer backbone end groups and / or polymer side chain end groups.

[0084]

[0143] Aryl groups include groups having one or more 5-, 6-, 7-, or 8-membered aromatic rings, including heteroaromatic rings. The term heteroaryl specifically refers to aryl groups having at least one 5-, 6-, 7-, or 8-membered heteroaromatic ring. Aryl groups can contain one or more fused heteroaromatic rings, and / or one or more fused aromatic rings, including combinations of one or more aromatic rings and one or more non-aromatic rings, which can be fused or linked via covalent bonds. Heteroaromatic rings can contain one or more N, O, or S atoms within the ring. Heteroaromatic rings can contain one, two, or three N atoms, one or two O atoms, and one or two S atoms, or a combination of one, two, or three N, O, or S atoms. Aryl groups are optionally substituted. Substituted aryl groups include, inter alia, those substituted with alkyl or alkenyl groups, which in turn can be optionally substituted. Specific aryl groups include phenyl, biphenyl, pyrrolidinyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, furyl, thienyl, pyridyl, quinolyl, isoquinolyl, pyridazinyl, pyrazinyl, indolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, pyridinyl, benzoxadiazolyl, benzothiadiazolyl, and naphthyl groups, all of which are optionally substituted. Substituted aryl groups include fully halogenated or semi-halogenated aryl groups, such as aryl groups in which one or more hydrogen atoms are replaced with one or more fluorine, chlorine, bromine, and / or iodine atoms. Substituted aryl groups include fully fluorinated or semi-fluorinated aryl groups, such as aryl groups in which one or more hydrogen atoms are replaced with one or more fluorine atoms.Aryl groups include, but are not limited to, aromatic or heteroaromatic groups corresponding to any one of the following: benzene, naphthalene, naphthoquinone, diphenylmethane, fluorene, anthracene, anthraquinone, phenanthrene, tetracene, tetracenedione, pyridine, quinoline, isoquinoline, indoles, isoindole, pyrrole, imidazole, oxazole, thiazole, pyrazole, pyrazine, pyrimidine, purine, benzimidazole, furans, benzofuran, dibenzofuran, carbazole, acridine, acridone, phenanthridine, thiophene, benzothiophene, dibenzothiophene, xanthene, xanthone, flavone, coumarin, azulene, or anthracycline. As used herein, groups corresponding to the groups listed above expressly include aromatic or heteroaromatic groups, including monovalent, divalent, and polyvalent groups of the aromatic and heteroaromatic groups listed herein, provided in a covalent configuration in the compounds of the present invention at any suitable point of attachment. In embodiments, aryl groups contain between 5 and 30 carbon atoms. In embodiments, aryl groups contain one 6-membered aromatic or heteroaromatic ring and one or more additional 5- or 6-membered aromatic or heteroaromatic rings. In embodiments, aryl groups contain between 5 and 18 carbon atoms in the ring. Aryl groups optionally have one or more aromatic or heteroaromatic rings with one or more electron-donating groups, electron-withdrawing groups, and / or targeting ligands as substituents. Some embodiments of the compositions of the present invention contain aryl groups as terminal groups, such as polymer backbone terminal groups and / or polymer side chain terminal groups.

[0085]

[0144] An arylalkyl group is an alkyl group substituted with one or more aryl groups, where the alkyl group optionally has additional substituents and the aryl group is optionally substituted. A particular alkylaryl group is a phenyl-substituted alkyl group, such as a phenylmethyl group. An alkylaryl group can alternatively be described as an aryl group substituted with one or more alkyl groups, where the alkyl group optionally has additional substituents and the aryl group is optionally substituted. A particular alkylaryl group is an alkyl-substituted phenyl group, such as methylphenyl. Substituted arylalkyl groups include fully halogenated or semi-halogenated arylalkyl groups, such as arylalkyl groups having one or more alkyl and / or aryl groups in which one or more hydrogens have been replaced with one or more fluorine, chlorine, bromine, and / or iodine atoms. The compositions of some embodiments of the present invention comprise arylalkyl groups as end groups, such as polymer backbone end groups and / or polymer side chain end groups.

[0086]

[0145] With respect to any of the groups described herein that contain one or more substituents, it is understood that such groups do not include any substitutions or substitution patterns that are sterically impractical and / or synthetically not feasible. Additionally, the compounds of the present invention include all stereochemical isomers arising from the substitution of these compounds. Optional substitution of an alkyl group includes substitution with one or more alkenyl groups, aryl groups, or both, in which the alkenyl or aryl group is optionally substituted. Optional substitution of an alkenyl group includes substitution with one or more alkyl groups, aryl groups, or both, in which the alkyl or aryl group is optionally substituted. Optional substitution of an aryl group includes substitution of the aryl ring with one or more alkyl groups, alkenyl groups, or both, in which the alkyl or alkenyl group is optionally substituted.

[0087]

[0146] Optional substituents on any of the alkyl, alkenyl and aryl groups include, inter alia, substitution with one or more of the following substituents: Halogens, including fluorine, chlorine, bromine or iodine; -CN-containing pseudohalides; -COOR (wherein R is hydrogen or an alkyl or aryl group, more particularly where R is a methyl, ethyl, propyl, butyl, or phenyl group, all of which groups are optionally substituted); -COR (wherein R is hydrogen or an alkyl or aryl group, more particularly where R is a methyl, ethyl, propyl, butyl, or phenyl group, all of which groups are optionally substituted); -CON(R)2, where each R, independently of the other R, is hydrogen or an alkyl or aryl group, more particularly where R is a methyl, ethyl, propyl, butyl, or phenyl group, all of which groups are optionally substituted; and where R and R can form a ring which can contain one or more double bonds and which can contain one or more additional carbon atoms; -OCON(R)2, where each R, independently of the other R, is hydrogen or an alkyl or aryl group, more particularly where R is a methyl, ethyl, propyl, butyl, or phenyl group, all of which groups are optionally substituted; and where R and R can form a ring which can contain one or more double bonds and which can contain one or more additional carbon atoms; -N(R)2, where each R, independently of the other R, is hydrogen, or an alkyl group, or an acyl group, or an aryl group, more particularly, where R is a methyl, ethyl, propyl, butyl, phenyl, or acetyl group, all of which are optionally substituted; and where R and R can form a ring which can contain one or more double bonds and which can contain one or more additional carbon atoms; -SR (wherein R is hydrogen or an alkyl or aryl group, more particularly where R is hydrogen, methyl, ethyl, propyl, butyl, or phenyl group, each of which is optionally substituted); -SOR, or -SOR (where R is an alkyl group or an aryl group, more particularly where R is a methyl, ethyl, propyl, butyl, or phenyl group, all of which are optionally substituted); -OCOOR (where R is an alkyl or aryl group); -SON(R) (wherein each R, independently of each other and R, is hydrogen, or an alkyl group, or an aryl group, all of which are optionally substituted, and where R and R can form a ring which can contain one or more double bonds and which can contain one or more additional carbon atoms); and

[0088]

[0147] -OR (where R is H, an alkyl group, an aryl group, or an acyl group, all of which are optionally substituted). In certain instances, R can be acyl, yielding -OCOR" (where R" is hydrogen or an alkyl group or an aryl group, more particularly, where R" is a methyl, ethyl, propyl, butyl, or phenyl group, all of which are optionally substituted).

[0089]

[0148] Particular substituted alkyl groups include haloalkyl groups, particularly trihalomethyl groups, and more particularly trifluoromethyl groups. Particular substituted aryl groups include mono-, di-, tri-, tetra-, and pentahalo-substituted phenyl groups; mono-, di-, tri-, tetra-, penta-, hexa-, and heptahalo-substituted naphthalene groups; 3- or 4-halo-substituted phenyl groups, 3- or 4-alkyl-substituted phenyl groups, 3- or 4-alkoxy-substituted phenyl groups, 3- or 4-RCO-substituted phenyl groups, and 5- or 6-halo-substituted naphthalene groups. More particularly, substituted aryl groups include acetylphenyl groups, particularly 4-acetylphenyl groups; fluorophenyl groups, particularly 3-fluorophenyl and 4-fluorophenyl groups; chlorophenyl groups, particularly 3-chlorophenyl and 4-chlorophenyl groups; methylphenyl groups, particularly 4-methylphenyl groups; and methoxyphenyl groups, particularly 4-methoxyphenyl groups.

[0090]

[0149] With respect to any of the above groups containing one or more substituents, it is understood that such groups do not contain any substitutions or substitution patterns that are sterically impractical and / or synthetically not feasible.

[0091]

[0150] Many of the molecules disclosed herein contain one or more ionizable groups. Ionizable groups include groups that can remove (e.g., -COOH) or add (e.g., amine) a proton, and groups that can be quaternized (e.g., amine). All possible ionic forms of such molecules and their salts are intended to be individually included in the disclosure herein. With respect to salts of the compounds herein, those skilled in the art can select from a wide variety of available counterions that are appropriate for preparing salts of the invention for a given application. In certain applications, the selection of a given anion or cation for preparing a salt may result in increased or decreased solubility of the salt.

[0092]

[0151] The compounds of the present invention may contain one or more chiral centers. Thus, the present invention is intended to include racemic mixtures, diastereomers, enantiomers, tautomers, and mixtures enriched in one or more stereoisomers. The scope of the present invention as described and claimed encompasses the racemic forms of the compounds as well as the individual enantiomers and non-racemic mixtures thereof.

[0093]

[0152] As used herein, the term "isomers" refers to compounds that have the same number and kinds of atoms, and hence the same molecular weight, but differ with respect to the structural arrangement or configuration of the atoms.

[0094]

[0153] The term "tautomer," as used herein, refers to one of two or more structural isomers that exist in equilibrium and are readily converted from one isomeric form to another. It will be apparent to one skilled in the art that certain compounds of the present invention may exist in tautomeric forms, and all such tautomeric forms of the compounds are within the scope of the present invention.

[0095]

[0154] Unless otherwise stated, structures depicted herein are also intended to include all stereochemical forms of the structure; i.e., the R and S configurations at each asymmetric center. Therefore, single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds are within the scope of the invention.

[0096]

[0155] Unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms, for example, the replacement of hydrogen by deuterium or tritium, or 13 C- or 14 Compounds having the present structure except for the replacement of a carbon by a C-enriched carbon are within the scope of this invention.

[0097]

[0156] The compounds of the present invention may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may contain isotopes of, for example, tritium ( 3 H), iodine-125( 125 I), or carbon-14 ( 14 C). All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0098]

[0157] symbol" [ka] " represents the point of attachment of one or more chemical moieties, one or more functional groups, one or more atoms, one or more ions, unpaired electrons, or one or more other chemical species to the depicted molecule, compound, or chemical formula. For example, [ka] In the formula, "X" represents a molecule or compound, and the symbol " [ka] 1750131972017_5.png represents the point of attachment of one or more chemical moieties, one or more functional groups, one or more atoms, one or more ions, unpaired electrons, or one or more other chemical species to X (where X corresponds to the depicted molecule, compound, or chemical formula) via a covalent bond, where the covalent bond can be any viable covalent bond, including, but not limited to, a single bond, a double bond, or a triple bond. Illustrative examples include the moiety [ka] wherein the carbon labeled "1" has a point of attachment that can be a double bond to another chemical species, such as a double bond to oxygen, or two single bonds to two independent chemical species, such as two separate single bonds to hydrogen. As another illustrative example, a moiety showing two points of attachment to the carbon labeled "1" is [ka] When two points of attachment are shown on a single atom of a molecule, such as in

[0026] , the shown points of attachment on the same single atom (e.g., carbon 1) can be interpreted as representing either a preferred embodiment of two separate bonds to that same single atom (e.g., two hydrogens bonded to carbon 1) or an optional embodiment of a single point of attachment to said same single atom (e.g., two points of attachment on carbon 1 can optionally be fixed as representing one double bond to carbon 1, such as a double bond to oxygen). As used herein, the various functional groups depicted will be understood to have a point of attachment at the functional group with a hyphen or dash (-), or a dash used in combination with an asterisk (*). In other words, in the case of -CH2CH2CH3 or -CH2CH2CH3, the point of attachment will be understood to be the left-most CH2 group. When a group is written without an asterisk or dash, the point of attachment is indicated by the clear and ordinary meaning of the described group.

[0099]

[0158] Where substituents are designated by their conventional chemical formula written from left to right, they equally encompass chemically identical substituents that would result from writing the structure from right to left, e.g., -CHO- is equivalent to -OCH-.

[0100]

[0159] The term "±" refers to an inclusive range of values, such that "X±Y" (where each of X and Y is independently a number) refers to an inclusive range of values ​​selected from the range of XY to X+Y. In the case of "X±Y" (where Y is a percentage (e.g., 1.0±20%)), the inclusive range of values ​​is selected from the range of XZ to X+Z (where Z is equal to X·(Y / 100)). For example, 1.0±20% refers to an inclusive range of values ​​selected from the range of 0.8 to 1.2.

[0101]

[0160] The term "and / or" is used in this specification, description, and claims to refer to only a single element and any combination of elements from the list in which the term "and / or" appears. A listing of two or more elements with the term "and / or" is a list of embodiments that includes embodiments having any of the individual elements only as well as embodiments having any combination of the listed elements. For example, the phrase "element A and / or element B" is a list of embodiments that is intended to include embodiments having only element A, only element B, and both elements A and B together. In other words, for example, the phrase "element A and / or element B" is equivalent to the phrase "element A, element B, or both element A and element B." Also, thus, for example, the phrase "element A, element B, and / or element C" is a list of embodiments that is intended to include embodiments having only element A, having only element B, having only element C, having elements A and B together, having elements A and C together, having elements B and C together, and having elements A, B, and C together.

[0102]

[0161] The term "melanin purity" can be used to characterize a collection or plurality of melanin materials (e.g., a plurality of types of artificial melanin nanoparticles, optionally a plurality of types of artificial melanin nanoparticles in a dispersion or formulation) and refers to a relative measure of the purity or content of a melanin type (e.g., pheomelanin) corresponding to a given melanin material relative to all types of melanin material (e.g., eumelanin, neuromelanin, pyomelanin, allomelanin, and pheomelanin) in the collection or plurality of melanin materials. The term "pheomelanin purity" refers to the relative purity or content of artificial melanin molecules and artificial melanin materials that are or contain pheomelanin (in a collection or plurality of melanin or melanin-containing molecules or materials), or artificial melanin polymers or their artificial melanin basic units, relative to all artificial melanin molecules and materials, or artificial melanin polymers or their artificial melanin basic units, in said collection or plurality of species. Melanin purity is a quantitative value selected from the range of 0 to 1.

[0103]

[0162] The term "polydispersity" or "dispersity" refers to a measure of the heterogeneity of particle sizes. For example, polydispersity can be used to characterize the width of a particle size distribution (e.g., particle size relative to number or frequency), such as the particle size distribution of artificial melanin nanoparticles. For example, polydispersity can characterize the heterogeneity of size of artificial melanin nanoparticles, such as artificial melanin nanoparticles in a solvent or artificial melanin nanoparticles in a dry state, such as those that form a film or layer. "Polydispersion index" is a measure of polydispersity. The polydispersity index can be measured, for example, using dynamic light scattering (DLS). Particles characterized by a polydispersity index of less than 0.1 are typically referred to as "monodisperse." For example, the polydispersity index (PDI) is the square of the standard deviation of the particle size distribution divided by its mean:

number

[0104]

[0163] The term "size-stable" refers to the stability of the particle size characteristics in a dispersion. Preferably, particles in a dispersion characterized as size-stable are characterized by size characteristics that are within 50%, 40%, 30%, preferably within 20%, more preferably within 15%, even more preferably within 10%, even more preferably within 5%, or the same as the reference or initial size characteristics under given conditions and optionally for a given time. For example, nanoparticles in a dispersion characterized as size-stable in a pH of at least 11, relative to the average size of nanoparticles in a dispersion with a pH of 7, have an average size in the pH 11 dispersion that is within 50%, 40%, 30%, preferably within 20%, more preferably within 15%, even more preferably within 10%, even more preferably within 5%, or the same as the average size of nanoparticles in an otherwise equivalent dispersion with a pH of 7. Preferably, but not necessarily, the nanoparticles are characterized as being size stable for a period of time that is at least 1 hour to 5 hours, preferably at least 5 hours to 12 hours, more preferably at least 12 hours to 1 week, and even more preferably at least 1 week.

[0105]

[0164] The term "self-assembly" refers to the process by which individual elements assemble into a network or organized structure without external guidance. In some embodiments, self-assembly leads to a decrease in the entropy of a system. In some embodiments, self-assembly may be triggered or initiated through contacting or reacting individual elements, optionally at a certain critical concentration, and / or through temperature and / or pressure. A "self-assembled structure" is a structure or network formed by self-assembly. In some embodiments, self-assembly is a polymer crystallization process. The Gibbs free energy of a self-assembled structure is lower than the sum of its individual components in its unorganized arrangement before self-assembly under otherwise identical conditions (e.g., temperature and pressure). In some embodiments, the entropy of a self-assembled structure is lower than the sum of its individual components in its unorganized arrangement before self-assembly under otherwise identical conditions (e.g., temperature and pressure). For example, the artificial melanin nanoparticles of the present disclosure can be formed by the self-assembly of multiple oligomers and / or melanin monomers. For example, structures or layers (eg, films) for the artificial melanin nanoparticles may be formed by self-assembly, such as structures or layers formed with the artificial melanin nanoparticles that exhibit structural color.

[0106]

[0165] As used herein, the terms "AMNP" and "ANP" are equivalent and interchangeable and refer to artificial allomelanin nanoparticles.

[0107]

[0166] As used herein, the terms "artificial" and "synthetic" with respect to melanin (e.g., "artificial melanin" and "synthetic melanin," respectively) are equivalent and interchangeable.

[0108]

[0167] As used herein, unless expressly stated otherwise, the term "NM" refers to nitrogen mustard, an exemplary chemical that induces damage to the skin.

[0109]

[0168] As used herein, the term "SMP" refers to synthetic (or artificial) melanin particles. In some embodiments and examples, the SMP is a synthetic / artificial polydopamine (PDA) particle. In some embodiments and examples, the SMP is a synthetic / artificial allomelanin (ANMP or ANP) particle.

[0110]

[0169] In certain embodiments, compositions or compounds of the invention, such as alloys or precursors to alloys, are isolated or substantially purified. In certain embodiments, isolated or purified compounds are at least partially isolated or substantially purified, as would be understood in the art. In certain embodiments, substantially purified compositions, compounds, or formulations of the invention have a chemical purity of 95% purity, optionally 99% for some uses, optionally 99.9% for some uses, optionally 99.99% for some uses, and optionally 99.999% for some uses.

[0111] Detailed Description of the Invention

[0170] In the following description, numerous specific details of the devices, device components and methods of the present invention are set forth in order to fully explain the precise nature of the invention. However, it will be apparent to those skilled in the art that the present invention may be practiced without these specific details.

[0112] Specific exemplary aspects and embodiments:

[0171] Various aspects are contemplated and disclosed herein, some of which are described in the following paragraphs. It is expressly contemplated and disclosed that any aspect or portion thereof can be combined to form an aspect. Additionally, it is expressly contemplated and disclosed that any reference to Aspect 1 includes a reference to Aspects 1a, 1b, 1c, 1d, and any combination thereof (i.e., any reference to an aspect includes a reference to a lettered version of that aspect). Furthermore, the terms "any preceding aspect" and "any one of the preceding aspects" refer to any aspect that appears before the aspect containing such phrases (e.g., the sentence "Aspect 15: ... a material, dispersion, formulation, or method according to any one of the preceding aspects" means that any aspect before Aspect 15, including lettered versions, is referenced). For example, it is contemplated and disclosed that, optionally, any composition, method, or formulation of any of the following aspects may be useful or combinable with any other aspect described below. Furthermore, for example, it is contemplated and disclosed that any of the embodiments or aspects described above can be optionally combined with any of the aspects listed below or any portion(s) thereof.

[0113]

[0172] Embodiment 1a: Comprises a surface functionalized with a modifier via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; A functionalized artificial melanin material, wherein the linker group is a nucleophilic group.

[0114]

[0173] Aspect 1b: one or more solvents (optionally one or more hydrophobic solvents); A functionalized artificial melanin material dispersed in one or more solvents. Including, The functionalized artificial melanin material comprises a surface functionalized with a modifier via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; A melanin-containing formulation, wherein the linker group is a nucleophilic group.

[0115]

[0174] Aspect 1c: A method for the treatment of a subject, comprising: topically administering a melanin preparation to the damaged skin of the subject; The functionalized artificial melanin material comprises a surface functionalized with a modifier via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; the linker group is a nucleophilic group; the melanin formulation comprises one or more solvents (optionally one or more hydrophobic solvents) and a functionalized artificial melanin material dispersed in the one or more solvents (optionally one or more hydrophobic solvents); the administered functionalized artificial melanin material comprises an extracellular functionalized artificial melanin material to the damaged skin; Promoting the healing of damaged skin at least through extracellular functionalized artificial melanin material; and wherein promoting skin healing comprises at least a portion of the extracellular artificial melanin material exerting a therapeutic extracellular activity.

[0116]

[0175] Aspect 1d: A method for preparing a functionalized artificial melanin material, comprising: providing non-functionalized artificial melanin nanoparticles; exposing the non-functionalized artificial melanin nanoparticles to a precursor of the modifier for a limited time; wherein the exposing step comprises: Conjugating non-functionalized artificial melanin nanoparticles with a precursor, thereby forming functionalized artificial melanin nanoparticles with a modifier. wherein the functionalized artificial melanin nanoparticles comprise a surface functionalized with a modifier via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; The method wherein the linker group is a nucleophilic group.

[0117]

[0176] Aspect 1e: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the formulation is non-aqueous, hydrophobic, or somewhere in between. Aspect 1f: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the formulation is non-aqueous and hydrophobic. Aspect 1g: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the formulation comprises both an aqueous solvent or phase and a non-aqueous or hydrophobic solvent or phase. Aspect 1h: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the formulation comprises both a hydrophilic solvent or phase and a hydrophobic solvent or phase. Aspect 1i: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by both the hydrophilic and hydrophobic phases of the formulation. Aspect 1j: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by a hydrophilic solvent or phase, a hydrophobic solvent or phase, or both a hydrophilic and a hydrophobic solvent or phase of the formulation. Aspect 1k: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by both one or more hydrophilic solvents and one or more hydrophobic solvents in the formulation. Aspect 11: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the formulation comprises one or more hydrophilic solvents, such as, but not necessarily limited to, water. Aspect 1m: The melanin-containing formulation of Aspect 1b or the method of Aspect 1c, wherein the formulation is characterized as intermediate between hydrophilic and hydrophobic. Aspect 1n: The melanin-containing formulation of aspect 1b or the method of aspect 1c, wherein the artificial melanin material (optionally being artificial melanin nanoparticles) is both hydrophilic or aqueous phase(s) and hydrophobic phase(s) and / or is intermediate between hydrophilic and hydrophobic such that it may be associated with or present within.Aspect 1o: The functionalized artificial melanin material, melanin-containing formulation, or method of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is characterized as intermediate between hydrophilic and hydrophobic such that it can be associated with, present in, or dispersed in both the hydrophilic or aqueous phase(s) and the hydrophobic phase(s). Aspect 1p: The functionalized artificial melanin material, melanin-containing formulation, or method of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is associated with, present in, or dispersed in one or more hydrophobic solvents of the formulation. Aspect 1q: The functionalized artificial melanin material, melanin-containing formulation, or method of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is associated with, present in, or dispersed in one or more hydrophobic solvents of the formulation. Aspect 1r: The functionalized artificial melanin material, melanin-containing formulation, or method of any one of the preceding aspects, wherein the artificial melanin material (optionally being artificial melanin nanoparticles) is associated with, present within, or dispersed in one or more hydrophilic solvents of the formulation.

[0118]

[0177] Aspect 2a: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, comprising functionalized artificial melanin nanoparticles, each functionalized artificial melanin nanoparticle independently comprising a surface that is functionalized with a modifier via a linker group. Aspect 2b: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, comprising functionalized artificial melanin nanoparticles, each functionalized artificial melanin nanoparticle independently comprising a surface that is functionalized with a modifier via a linker group.

[0119]

[0178] Aspect 3: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the linker group is an amine group, a thiol group, or any combination thereof.

[0120]

[0179] Aspect 4: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the linker group is an amine group.

[0121]

[0180] Aspect 5: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the linker group is a primary amine group.

[0122]

[0181] Embodiment 6: The linker group has the formula FX1A or FX1B: [ka] 10. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, characterized by:

[0123]

[0182] Aspect 7a: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the functional group is hydrophobic or confers at least partial hydrophobicity to the functionalized artificial melanin material or to the functionalized artificial melanin nanoparticles thereof.

[0124]

[0183] Aspect 8a: The functionalized artificial melanin material is hydrophobic and / or forms a stable colloid in a non-aqueous hydrophobic solvent at a concentration of said material selected from the range of about 0.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 2.0 mg / mL to about 100 mg / mL, optionally selected from the range of about 2.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 75 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 75 mg / mL,

[0039] The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein any range and value therebetween is optionally selected from the range of about 1.0 mg / mL to about 50 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 40 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 30 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 20 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 10 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 5 mg / mL, etc., is expressly contemplated, inclusively, and is disclosed herein.Aspect 8b: The functionalized artificial melanin material is characterized as intermediate between hydrophilic and hydrophobic, such that the functionalized artificial melanin material is configured to be associated with, present within, or dispersed in both hydrophilic or aqueous phase(s) and hydrophobic phase(s), such that the functionalized artificial melanin material forms a stable colloidal solution or formulation having hydrophilic or aqueous phase(s), hydrophobic phase(s), or both, when the concentration of said material in said colloidal solution or formulation is selected from the range of about 0.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 2.0 mg / mL to about 100 mg / mL. 2.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 75 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 50 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 40 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 30 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 20 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 10 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 5 mg / mL, etc., and any ranges and values ​​therebetween are expressly contemplated, inclusive, and disclosed herein.

[0125]

[0184] Aspect 9: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein a dispersion or formulation having the functionalized artificial melanin material or functionalized artificial melanin nanoparticles thereof at a concentration selected from the range of 0.5 mg / mL to 100 mg / mL is characterized by a contact angle of at least approximately 90°, optionally at least approximately 100°, optionally at least approximately 105°, optionally at least approximately 110°, optionally at least approximately 115°, optionally at least approximately 120°, optionally at least approximately 125°, optionally at least approximately 130°, optionally at least approximately 135°, optionally at least approximately 140°, optionally at least approximately 145°, optionally at least approximately 150°, optionally at least approximately 155°, or optionally at least approximately 160°.

[0126]

[0185] Aspect 10: A dispersion or formulation having the functionalized artificial melanin material or functionalized artificial melanin nanoparticles thereof at a concentration selected from the range of 0.5 mg / mL to 100 mg / mL is selected from the range of about 115° to about 180°, optionally selected from the range of about 120° to about 180°, optionally selected from the range of about 125° to about 180°, optionally selected from the range of about 130° to about 180°, optionally selected from the range of about 135° to about 180°, optionally selected from the range of about 140° to about 180°, optionally selected from the range of about 145° to about 180°, or optionally selected from the range of about 150° to about 180°. 160°、170°、180°、190°、200°、210°、220°、230°、240°、250°、260°、270°、280°、290°、300°、310°、320°、330°、340°、350°、360°、370°、380°、400°、410°、420°、430°、440°、450°、460°、470°、500°、510°、520°、530°、540°、550°、560°、600°、700°、800°、900°、900°、1000°、1100°、1200°、130°、140°、150°、160°、170°、210°、220°、230°、140°、150°、240°、160°、250°、320°、260°、330°、140°、150°、270°、340°、280°、350°、360°、370°、410°、520°、530°、140°、150°、280°、290°、340°、150°、290°、350°、360°、370°、380°、410°、420°、430°、440°、150°、280°、380°、420°、430°、440°、150°、280°、390°、450°、460°、470°、480°、51

[0127]

[0186] Aspect 11: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functionalized artificial melanin material or functionalized artificial melanin nanoparticles thereof, when dispersed in water and / or a non-aqueous hydrophobic solvent at a concentration selected from the range of 0.5 mg / mL to 100 mg / mL, has a zeta potential of -40 mV or greater (optionally approximately -35 mV or greater, optionally approximately -30 mV or greater, optionally approximately -25 mV or greater, optionally approximately -20 mV or greater, optionally approximately -15 mV or greater, optionally approximately -10 mV or greater, optionally approximately -5 mV or greater, optionally approximately 5 mV or greater, optionally approximately 10 mV or greater, optionally approximately 15 mV or greater, optionally approximately 20 mV or greater).

[0128]

[0187] Embodiment 12: The modifying agent has formula FX2A or FX2B: [ka] (wherein X is a functional group) 10. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, characterized by:

[0129]

[0188] Aspect 13: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein each linker group is independently attached to a phenyl group or a quinone of the artificial melanin material, or of each artificial melanin nanoparticle.

[0130]

[0189] Aspect 14: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the modifier attached to the artificial melanin material or to the respective functionalized artificial melanin nanoparticle is a product of a Michael addition or via a Schiff base reaction.

[0131]

[0190] Aspect 15: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the linker group of the modifier is attached to the outer surface of the functionalized artificial melanin material or to the functionalized artificial melanin nanoparticles thereof, attached to the inner pore surface of the functionalized artificial melanin material or to the functionalized artificial melanin nanoparticles thereof, or both.

[0132]

[0191] Aspect 16: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein at least a portion of the functionalized artificial melanin material or functionalized artificial melanin nanoparticles thereof comprise at least two different modifiers.

[0133]

[0192] Aspect 17a: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the material comprises at least 5% by weight of a modifier. Aspect 17b: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the material comprises at least 5% by weight and less than 75% by weight of a modifier.

[0134]

[0193] Aspect 18: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the functional group faces the solution or environment to which the functionalized artificial melanin material, or the functionalized artificial melanin nanoparticles thereof, are exposed.

[0135]

[0194] Aspect 19a: The functional group is a substituted or unsubstituted C-C 30 Hydrocarbyl groups, substituted or unsubstituted C4-C 30 Alkyl groups, substituted or unsubstituted C4-C 30 Cycloalkyl groups, substituted or unsubstituted C4-C 30 Aryl groups, substituted or unsubstituted C4-C 30 Heteroaryl groups, substituted or unsubstituted C4-C 30 Acyl groups, substituted or unsubstituted C4-C 30 Alkoxy groups, substituted or unsubstituted C4-C 30 Alkenyl groups, substituted or unsubstituted C4-C 30Alkynyl groups, substituted or unsubstituted C4-C 30 Aspect 19b: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is selected from the group consisting of a substituted or unsubstituted C4-C 30 Hydrocarbyl groups, substituted or unsubstituted C4-C 30 Alkyl groups, substituted or unsubstituted C4-C 30 Cycloalkyl groups, substituted or unsubstituted C4-C 30 Aryl groups, substituted or unsubstituted C4-C 30 Heteroaryl groups, substituted or unsubstituted C4-C 30 Acyl groups, substituted or unsubstituted C4-C 30 Alkoxy groups, substituted or unsubstituted C4-C 30 Alkenyl groups, substituted or unsubstituted C4-C 30 Alkynyl groups, substituted or unsubstituted C4-C 30 10. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, comprising an alkylaryl group, an alkylaryl group, or any combination thereof.

[0136]

[0195] Aspect 20a: The functional group is C4-C 30 Alkyl groups, C4-C 30 Alkenyl groups, C4-C 30 Aspect 20b: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is selected from the group consisting of a C4-C 30 Alkyl groups, C4-C 30 Alkenyl groups, C4-C 30 3. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functionalized artificial melanin material, dispersion, melanin-containing formulation, or method is selected from the group consisting of: a methyl group, a methyl group, an alkynyl ...

[0137]

[0196] Aspect 21a: The functional group is a substituted or unsubstituted C-C 30Aspect 21b: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C-C 24 Aspect 21c: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C-C 20 The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C-C 18 The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C-C 30 Aspect 21f: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C8-C 24 Aspect 21g: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C 12 ~C 30 Aspect 21h: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C 12 ~C 24 Aspect 21i: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C 12 ~C 20 10. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functionalized artificial melanin is a hydrocarbyl group.

[0138]

[0197] Aspect 22a: The functional group is a substituted or unsubstituted C-C 30Aspect 22b: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C-C alkyl group. 24 Aspect 22c: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C6-C 20 Aspect 22d: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C6-C 18 Aspect 22e: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C8-C 30 Aspect 22f: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C8-C 24 Aspect 22g: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C 12 ~C 30 Aspect 22h: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C 12 ~C 24 Aspect 22i: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is a substituted or unsubstituted C 12 ~C 20 10. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the alkyl group is an alkyl group.

[0139]

[0198] Aspect 23: The functional group is a substituted or unsubstituted C-C 24 10. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the alkyl group is an alkyl group.

[0140]

[0199] Aspect 24a: The functional group is a substituted or unsubstituted C-C 30 Hydrocarbyl groups, substituted or unsubstituted C4-C 30 Alkyl groups, substituted or unsubstituted C4-C 30 Cycloalkyl groups, substituted or unsubstituted C4-C 30 Aryl groups, substituted or unsubstituted C4-C 30 Heteroaryl groups, substituted or unsubstituted C4-C 30 Acyl groups, substituted or unsubstituted C4-C 30 Alkoxy groups, substituted or unsubstituted C4-C 30 Alkenyl groups, substituted or unsubstituted C4-C 30 Alkynyl groups, substituted or unsubstituted C4-C 30 Aspect 24b: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is selected from the group consisting of an alkylaryl group, a substituted or unsubstituted hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted sulfide group, a substituted or unsubstituted thiol group, a substituted or unsubstituted phosphate group, a substituted or unsubstituted azo group, a substituted or unsubstituted cyanate group, a substituted or unsubstituted primary amine group, a substituted or unsubstituted secondary amine group, a substituted or unsubstituted tertiary group, a substituted or unsubstituted imine group, a substituted or unsubstituted nitrile group, a substituted or unsubstituted pyridinyl group, a substituted or unsubstituted diamine group, a substituted or unsubstituted triamine group, a substituted or unsubstituted azide group, a substituted or unsubstituted diimine group, a substituted or unsubstituted triimine group, a substituted or unsubstituted amide group, a substituted or unsubstituted diimide group, a substituted or unsubstituted ether group, and any combination thereof. 30 Hydrocarbyl groups, substituted or unsubstituted C4-C 30 Alkyl groups, substituted or unsubstituted C4-C 30 Cycloalkyl groups, substituted or unsubstituted C4-C 30 Aryl groups, substituted or unsubstituted C4-C 30 Heteroaryl groups, substituted or unsubstituted C4-C 30 Acyl groups, substituted or unsubstituted C4-C 30 Alkoxy groups, substituted or unsubstituted C4-C 30 Alkenyl groups, substituted or unsubstituted C4-C 30 Alkynyl groups, substituted or unsubstituted C4-C30 2. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, comprising an alkylaryl group, a substituted or unsubstituted hydroxyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted sulfide group, a substituted or unsubstituted thiol group, a substituted or unsubstituted phosphate group, a substituted or unsubstituted azo group, a substituted or unsubstituted cyanate group, a substituted or unsubstituted primary amine group, a substituted or unsubstituted secondary amine group, a substituted or unsubstituted tertiary group, a substituted or unsubstituted imine group, a substituted or unsubstituted nitrile group, a substituted or unsubstituted pyridinyl group, a substituted or unsubstituted diamine group, a substituted or unsubstituted triamine group, a substituted or unsubstituted azide group, a substituted or unsubstituted diimine group, a substituted or unsubstituted triimine group, a substituted or unsubstituted amido group, a substituted or unsubstituted diimide group, a substituted or unsubstituted ether group, or any combination thereof.

[0141]

[0200] Aspect 25a: The functional group is a substituted or unsubstituted C-C 30 Hydrocarbyl groups, substituted or unsubstituted C4-C 30 Alkyl groups, substituted or unsubstituted C4-C 30 Cycloalkyl groups, substituted or unsubstituted C4-C 30 Aryl groups, substituted or unsubstituted C4-C 30 Heteroaryl groups, substituted or unsubstituted C4-C 30 Acyl groups, substituted or unsubstituted C4-C 30 Alkoxy groups, substituted or unsubstituted C4-C 30 Alkenyl groups, substituted or unsubstituted C4-C 30 Alkynyl groups, substituted or unsubstituted C4-C 30 Aspect 25b: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functional group is selected from the group consisting of an alkylaryl group, a substituted or unsubstituted primary amine group, a substituted or unsubstituted secondary amine group, a substituted or unsubstituted tertiary amine group, and any combination thereof. 30 Hydrocarbyl groups, substituted or unsubstituted C4-C 30 Alkyl groups, substituted or unsubstituted C4-C 30Cycloalkyl groups, substituted or unsubstituted C4-C 30 Aryl groups, substituted or unsubstituted C4-C 30 Heteroaryl groups, substituted or unsubstituted C4-C 30 Acyl groups, substituted or unsubstituted C4-C 30 Alkoxy groups, substituted or unsubstituted C4-C 30 Alkenyl groups, substituted or unsubstituted C4-C 30 Alkynyl groups, substituted or unsubstituted C4-C 30 2. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, comprising an alkylaryl group, a substituted or unsubstituted primary amine group, a substituted or unsubstituted secondary amine group, a substituted or unsubstituted tertiary amine group, or any combination thereof.

[0142]

[0201] Aspect 26: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein each modifier is independently selected from the group consisting of 1-hexylamine, 3,3-dimethylbutylamine, octadecylamine, 5-amino-1-pentanol, t-butylamine, 10-amino-1-decanol, 1,6-hexanediamine, and 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononylamine.

[0143]

[0202] Aspect 27: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, wherein the functionalized artificial melanin material comprises an amorphous functionalized artificial melanin material.

[0144]

[0203] Aspect 28: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein each of the functionalized artificial melanin material or functionalized artificial melanin nanoparticles thereof is not bound to, conjugated to, attached to, coated by, encapsulated by, or otherwise chemically associated with a natural or biological proteinaceous matrix, component, or lipid.

[0145]

[0204] Aspect 29: The functionalized artificial melanin material or its functionalized artificial melanin nanoparticles, respectively, are characterized as eumelanin, pheomelanin, allomelanin, or a combination thereof, in the functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects.

[0146]

[0205] Aspect 30: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the functionalized artificial melanin material comprises artificial allomelanin nanoparticles, artificial polydopamine nanoparticles, or any combination thereof.

[0147]

[0206] Aspect 31: The functionalized artificial melanin material or its functionalized artificial melanin nanoparticles are porous and have a Brunauer-Emmett-Teller (BET) surface area selected from the range of 70 m 2 / g to 800 m 2 / g, with any range and value therebetween being explicitly contemplated and disclosed herein, in the functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects.

[0148]

[0207] Aspect 32: The functionalized artificial melanin material or its functionalized artificial melanin nanoparticles are non-porous or have a Brunauer-Emmett-Teller (BET) surface area of less than 20 m 2 / g, with any range and value less than 20 m 2 / g being explicitly contemplated and disclosed herein, in the functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects.

[0149]

[0208] Aspect 33: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the functionalized artificial melanin material comprises functionalized artificial melanin particles having an average cross-sectional size, as measured by transmission electron microscopy and / or dynamic light scattering, selected from the range of 10 nm to 1000 nm, any range and value therebetween being expressly contemplated and disclosed herein.

[0150]

[0209] Aspect 34: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the functionalized artificial melanin material comprises functionalized artificial melanin particles having an average cross-sectional size, as measured by transmission electron microscopy and / or dynamic light scattering, selected from the ranges of 10 nm to 100 nm, 100 nm to 500 nm, or a combination thereof.

[0151]

[0210] Aspect 35: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, characterized by a DPPH radical scavenging activity of at least 30% per 50 μg of functionalized artificial melanin material.

[0152]

[0211] Embodiment 36: The functionalized artificial melanin material of any one of the preceding embodiments, which is a thin film.

[0153]

[0212] Embodiment 37: The functionalized artificial melanin material of any one of the preceding embodiments, wherein the material is a thin film, and the thin film exhibits structural color.

[0154]

[0213] Aspect 38: A functionalized artificial melanin material according to any one of the preceding aspects, which is a thin film, the thin film comprising one or more monolayers of the functionalized artificial melanin nanoparticles.

[0155]

[0214] Aspect 39: A functionalized artificial melanin material according to any one of the preceding aspects, which is a thin film, the thin film comprising one, two, three, or four monolayers of the functionalized artificial melanin nanoparticles.

[0156]

[0215] Embodiment 40: The functionalized artificial melanin material of any one of the preceding embodiments, which is a thin film, the thin film being at a liquid-liquid interface, a liquid-gas interface, or on a substrate.

[0157]

[0216] Aspect 41: A thin film, the thin film being 0.25 cm 2 ~9cm 2 10. The functionalized artificial melanin material of any one of the preceding aspects, having an area selected from the range of:

[0158]

[0217] Embodiment 42: The functionalized artificial melanin material of any one of the preceding embodiments, wherein the material is a thin film, and the thin film is on the skin.

[0159]

[0218] Embodiment 43: one or more solvents (optionally one or more hydrophobic solvents); a functionalized artificial melanin material according to any one of the preceding aspects dispersed in one or more solvents; A melanin-containing preparation comprising:

[0160]

[0219] Embodiment 44a: one or more solvents (optionally one or more hydrophobic solvents); A functionalized artificial melanin material dispersed in one or more solvents. Including, The functionalized artificial melanin material comprises a surface functionalized with a modifier via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; A melanin-containing formulation, wherein the linker group is a nucleophilic group.

[0161]

[0220] Aspect 44b: The melanin-containing formulation of any one of the preceding aspects, which is non-aqueous, hydrophobic, or intermediate therebetween. Aspect 44c: The melanin-containing formulation of any one of the preceding aspects, which is non-aqueous and hydrophobic. Aspect 44d: The melanin-containing formulation of any one of the preceding aspects, which comprises both an aqueous solvent or phase and a non-aqueous or hydrophobic solvent or phase. Aspect 44e: The melanin-containing formulation of any one of the preceding aspects, which comprises both a hydrophilic solvent or phase and a hydrophobic solvent or phase. Aspect 44f: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by both the hydrophilic and hydrophobic phases of the formulation. Aspect 44g: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by the hydrophilic solvent or phase, the hydrophobic solvent or phase, or both the hydrophilic and hydrophobic solvents or phases of the formulation. Aspect 44h: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by both one or more hydrophilic solvents and one or more hydrophobic solvents in the formulation. Aspect 44i: The melanin-containing formulation of any one of the preceding aspects, comprising one or more hydrophilic solvents, such as but not necessarily limited to water. Aspect 44j: The melanin-containing formulation of any one of the preceding aspects, characterized as intermediate between hydrophilic and hydrophobic. Aspect 44k: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is intermediate between hydrophilic and hydrophobic such that it may be associated with or present in both the hydrophilic or aqueous phase(s) and the hydrophobic phase(s). Aspect 441: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally being artificial melanin nanoparticles) is characterized as intermediate between hydrophilic and hydrophobic such that it can be associated with, present in, or dispersed in both hydrophilic or aqueous phase(s) and hydrophobic phase(s).Aspect 44m: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is associated with, present in, or dispersed in one or more hydrophobic solvents of the formulation. Aspect 44n: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is associated with, present in, or dispersed in one or more hydrophobic solvents of the formulation. Aspect 44o: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is associated with, present in, or dispersed in one or more hydrophilic solvents of the formulation.

[0162]

[0221] Aspect 45: The melanin-containing formulation of any one of the preceding aspects, wherein the functionalized artificial melanin material comprises functionalized artificial melanin nanoparticles, each functionalized artificial melanin nanoparticle independently comprising a surface functionalized with a modifying agent via a linker group.

[0163]

[0222] Embodiment 46: The concentration of the artificial melanin material in the melanin formulation is selected from the range of about 0.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 2.0 mg / mL to about 100 mg / mL, optionally selected from the range of about 2.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 75 mg / mL, or optionally selected from the range of about 1.0 mg / mL to about 50 mg / mL. 1.0 mg / mL to about 40 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 30 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 20 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 10 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 5 mg / mL, etc., with any value and range therebetween expressly contemplated and disclosed herein.

[0164]

[0223] Aspect 47: The melanin-containing formulation of any one of the preceding aspects, wherein the concentration of the functionalized artificial melanin nanoparticles is selected from the range of approximately 0.5 mg / mL to approximately 100 mg / mL, with any value and range therebetween being expressly contemplated and disclosed herein.

[0165]

[0224] Embodiment 48: The melanin-containing formulation of any one of the preceding embodiments, characterized by a contact angle of at least approximately 90°, optionally at least 100°, optionally at least 105°, optionally at least 110°, optionally at least 115°, optionally at least 120°, optionally at least 125°, optionally at least 130°, optionally at least 135°, optionally at least 140°, optionally at least 145°, optionally at least 150°, optionally at least 155°, optionally at least approximately 160°.

[0166]

[0225] Embodiment 49: Selected from the range of approximately 115° to approximately 180°, optionally selected from the range of approximately 120° to approximately 180°, optionally selected from the range of 125° to 180°, optionally selected from the range of 130° to 180°, optionally selected from the range of 135° to 180°, optionally selected from the range of 140° to 180°, optionally selected from the range of 145° to 180°, optionally selected from the range of 150° to 180°, optionally selected from the range of 155° to 180° 10. The melanin-containing formulation of any one of the preceding aspects, characterized by a contact angle optionally selected from the range of 115° to 160°, optionally selected from the range of 120° to 160°, optionally selected from the range of 125° to 160°, optionally selected from the range of 130° to 160°, optionally selected from the range of 135° to 160°, optionally selected from the range of 140° to 160°, or optionally selected from the range of 145° to 180°.

[0167]

[0226] Embodiment 50: The melanin-containing formulation of any one of the preceding embodiments, wherein the dispersed functionalized artificial melanin nanoparticles are characterized by a zeta potential magnitude of greater than approximately 20.

[0168]

[0227] Embodiment 51: The melanin-containing formulation of any one of the preceding embodiments, wherein the dispersed functionalized artificial melanin nanoparticles are characterized by a zeta potential of about −40 mV or greater, optionally about −35 mV or greater, optionally about −30 mV or greater, optionally about −25 mV or greater, optionally about −20 mV or greater, optionally about −15 mV or greater, optionally about −10 mV or greater, optionally about −5 mV or greater, optionally about 5 mV or greater, optionally about 10 mV or greater, optionally about 15 mV or greater, optionally about 20 mV or greater.

[0169]

[0228] Embodiment 52: The melanin-containing formulation of any one of the preceding embodiments, wherein the dispersed functionalized artificial melanin nanoparticles are characterized by a positive zeta potential.

[0170]

[0229] Embodiment 53: The melanin-containing formulation of any one of the preceding embodiments, wherein the melanin-containing formulation is characterized as a stable colloid.

[0171]

[0230] Aspect 54: The melanin-containing formulation of any one of the preceding aspects, which is an ointment, cream, gel, paste, or any combination thereof.

[0172]

[0231] Embodiment 55: The melanin-containing formulation of any one of the preceding embodiments, wherein the one or more hydrophobic solvents are organic solvents.

[0173]

[0232] Embodiment 56: The melanin-containing formulation of any one of the preceding embodiments, wherein the one or more hydrophobic solvents constitute at least approximately 60%, optionally at least 65%, optionally at least 70%, optionally at least 75%, optionally at least 80%, optionally at least 85%, optionally at least 95%, optionally at least 95% of the total solvent concentration in the formulation.

[0174]

[0233] Embodiment 57: The melanin-containing formulation of any one of the preceding embodiments, wherein the one or more hydrophobic solvents represent at least approximately 60%, optionally at least 65%, optionally at least 70%, optionally at least 75%, optionally at least 80%, optionally at least 85%, optionally at least 95%, optionally at least 95% of the formulation.

[0175]

[0234] Embodiment 58: The melanin-containing formulation of any one of the preceding embodiments, having no more than about 40 vol.% water, optionally no more than about 35 vol.% water, optionally no more than about 30 vol.% water, optionally no more than about 25 vol.% water, optionally no more than about 20 vol.% water, optionally no more than about 15 vol.% water, optionally no more than about 10 vol.% water, optionally no more than about 5 vol.% water, optionally no more than about 1 vol.% water.

[0176]

[0235] Aspect 59: The melanin-containing formulation of any one of the preceding aspects, wherein the one or more hydrophobic solvents comprise dichloromethane, chloroform, tetrahydrofuran, toluene, ethyl acetate, hexane, cyclohexane, squalene, squalene, petrolatum, a petrolatum-containing solvent or solvent mixture, petrolatum ointment, a petrolatum-based ointment, or any combination thereof.

[0177]

[0236] Aspect 60: The melanin-containing formulation of any one of the preceding aspects, wherein the one or more hydrophobic solvents comprise petrolatum or petrolatum.

[0178]

[0237] Embodiment 61: The melanin-containing formulation of any one of the preceding embodiments, comprising an organogel.

[0179]

[0238] Embodiment 62: The melanin-containing formulation of any one of the preceding embodiments, wherein the one or more hydrophobic solvents is a solvent formulation suitable as a carrier for wound healing.

[0180]

[0239] Aspect 63a: The melanin-containing formulation of any one of the preceding aspects, which is a sunscreen or sunblock product for application to the skin; wherein a functionalized artificial melanin material is provided in the formulation to promote skin healing in the event of UV-induced skin damage. Aspect 63b: The melanin-containing formulation of any one of the preceding aspects, which is an additive in a sunscreen or sunblock product for application to the skin; wherein a functionalized artificial melanin material is provided in the formulation to promote skin healing in the event of UV-induced skin damage.

[0181]

[0240] Aspect 64: The melanin-containing formulation of any one of the preceding aspects, having a viscosity selected from the range of approximately 12 cP to approximately 64,000 cP at 25°C as measured using a viscometer and / or rheometer.

[0182]

[0241] Embodiment 65: The melanin-containing formulation of any one of the preceding embodiments, which is therapeutically effective in promoting skin healing when administered to damaged skin.

[0242] Embodiment 66: A method for treatment of a subject, comprising: topically administering to damaged skin of a subject a melanin formulation according to any one of the preceding aspects; a melanin formulation comprising the functionalized artificial melanin material of any one of the preceding aspects; the administered functionalized artificial melanin material comprises an extracellular functionalized artificial melanin material to the damaged skin; Promoting the healing of damaged skin at least through extracellular functionalized artificial melanin material; promoting skin healing includes at least a portion of the extracellular artificial melanin material exerting a therapeutic extracellular activity; A method comprising:

[0183]

[0243] Aspect 67a: A method for treating a subject, comprising: topically administering a melanin preparation to the damaged skin of the subject; The functionalized artificial melanin material comprises a surface functionalized with a modifier via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; the linker group is a nucleophilic group; the melanin formulation comprises one or more solvents (optionally one or more hydrophobic solvents) and a functionalized artificial melanin material dispersed in the one or more hydrophobic solvents; the administered functionalized artificial melanin material comprises an extracellular functionalized artificial melanin material to the damaged skin; Promoting the healing of damaged skin at least through extracellular functionalized artificial melanin material; promoting skin healing includes at least a portion of the extracellular artificial melanin material exerting a therapeutic extracellular activity; A method comprising:

[0184]

[0244] Aspect 67b: The melanin-containing formulation of any one of the preceding aspects, which is non-aqueous, hydrophobic, or intermediate therebetween. Aspect 67c: The melanin-containing formulation of any one of the preceding aspects, which is non-aqueous and hydrophobic. Aspect 67d: The melanin-containing formulation of any one of the preceding aspects, which comprises both an aqueous solvent or phase and a non-aqueous or hydrophobic solvent or phase. Aspect 67e: The melanin-containing formulation of any one of the preceding aspects, which comprises both a hydrophilic solvent or phase and a hydrophobic solvent or phase. Aspect 67f: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by both the hydrophilic and hydrophobic phases of the formulation. Aspect 67g: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by the hydrophilic solvent or phase, the hydrophobic solvent or phase, or both the hydrophilic and hydrophobic solvents or phases of the formulation. Aspect 67h: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is dispersed by both one or more hydrophilic solvents and one or more hydrophobic solvents in the formulation. Aspect 67i: The melanin-containing formulation of any one of the preceding aspects, comprising one or more hydrophilic solvents, such as but not necessarily limited to water. Aspect 67j: The melanin-containing formulation of any one of the preceding aspects, characterized as intermediate between hydrophilic and hydrophobic. Aspect 67k: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is intermediate between hydrophilic and hydrophobic such that it may be associated with or present in both the hydrophilic or aqueous phase(s) and the hydrophobic phase(s). Aspect 671: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally being artificial melanin nanoparticles) is characterized as intermediate between hydrophilic and hydrophobic such that it can be associated with, present in, or dispersed in both hydrophilic or aqueous phase(s) and hydrophobic phase(s).Aspect 67m: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is associated with, present in, or dispersed in one or more hydrophobic solvents of the formulation. Aspect 67n: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is associated with, present in, or dispersed in one or more hydrophobic solvents of the formulation. Aspect 67o: The melanin-containing formulation of any one of the preceding aspects, wherein the artificial melanin material (optionally artificial melanin nanoparticles) is associated with, present in, or dispersed in one or more hydrophilic solvents of the formulation.

[0185]

[0245] Embodiment 68: A method for treatment according to any one of the preceding embodiments, wherein the functionalized artificial melanin material comprises functionalized artificial melanin nanoparticles, each functionalized artificial melanin nanoparticle independently comprising a surface functionalized with a modifying agent via a linker group.

[0186]

[0246] Embodiment 69: A method for treatment according to any one of the preceding embodiments, wherein the damaged skin is a closed wound, an open wound, or both.

[0187]

[0247] Embodiment 70: A method for treatment according to any one of the preceding embodiments, wherein the damaged skin is associated with thermally induced damage, chemically induced damage, radiation induced damage, mechanical friction damage, and / or infected cellulitis induced damage.

[0188]

[0248] Embodiment 71: A method for treatment according to any one of the preceding embodiments, wherein the radiation-induced damage is UV-induced damage and the chemically-induced damage is mustard-induced (optionally nitrogen mustard-induced) damage.

[0189]

[0249] Embodiment 75: A method for treatment according to any one of the preceding embodiments, wherein the damaged skin comprises one or more of blisters, vesicles, and denuded skin.

[0190]

[0250] Embodiment 73: A method for treatment according to any one of the preceding embodiments, wherein at least a portion of the extracellular melanin material is within the stratum corneum of the damaged skin.

[0191]

[0251] Embodiment 74: A method for treatment according to any one of the preceding embodiments, wherein the damaged skin comprises extracellular free radical species; and the therapeutic extracellular activity comprises at least a portion of the extracellular artificial melanin material quenching at least the extracellular free radical species.

[0192]

[0252] Embodiment 75: A method for treatment according to any one of the preceding embodiments, wherein the extracellular free radical species comprise reactive oxygenated species.

[0193]

[0253] Embodiment 76: A method for treatment according to any one of the preceding embodiments, wherein at least a portion of the quenched extracellular free radical species are within the stratum corneum.

[0194]

[0254] Aspect 77: A method for treatment of any one of the preceding aspects, wherein the damaged skin comprises inflammation; and the step of promoting skin healing comprises at least a portion of the administered artificial melanin material directly and / or indirectly reducing the inflammation.

[0195]

[0255] Aspect 78: A method for treatment according to any one of the preceding aspects, wherein the therapeutic extracellular activity comprises at least a portion of the extracellular artificial melanin material directly and / or indirectly reducing inflammation.

[0196]

[0256] Aspect 79: The method for treatment of any one of the preceding aspects, wherein directly and / or indirectly reducing inflammation comprises at least a portion of the administered artificial melanin adsorbing one or more inflammatory factors, one or more factors, one or more scarring and / or fibrosis factors, or any combination thereof.

[0197]

[0257] Aspect 80: The method for treatment of any one of the preceding aspects, wherein directly and / or indirectly reducing inflammation comprises at least a portion of the extracellular artificial melanin adsorbing one or more extracellular inflammatory factors, one or more extracellular enzymatic factors, one or more extracellular scarring and / or fibrosis factors, or any combination thereof.

[0198]

[0258] Embodiment 81: A method for treatment according to any one of the preceding embodiments, wherein the one or more inflammatory and / or one or more enzymatic factors comprise TNFα, iNOS, MMP9, MMP3, MMP9, CXCL1, one or more proteins associated with the MAPK / ERK pathway, and / or one or more enzymes associated with the MAPK / ERK pathway.

[0199]

[0259] Embodiment 82: A method for treatment according to any one of the preceding embodiments, wherein at least a portion of the adsorbed inflammatory factor and / or the adsorbed extracellular enzymatic factor is within the stratum corneum.

[0200]

[0260] Aspect 83: A method for treatment described in any one of the preceding aspects, wherein the promoting step comprises at least a portion of the administered artificial melanin directly and / or indirectly downregulating inflammation-related genes and / or apoptosis-related genes and / or collagen-degrading enzymes and / or fibroblast scarring and fibrosis genes compared to when the artificial melanin material is not present.

[0201]

[0261] Aspect 84: A method for treatment described in any one of the preceding aspects, wherein the promoting step includes at least a portion of the administered artificial melanin directly and / or indirectly inhibiting apoptosis compared to when the artificial melanin material is not present.

[0202]

[0262] Embodiment 85: A method for treatment according to any one of the preceding embodiments, wherein at least 50% of the administered artificial melanin material is extracellular artificial melanin material.

[0203]

[0263] Embodiment 86: A method for treatment according to any one of the preceding embodiments, wherein the extracellular artificial melanin material is present extracellularly as long as it is present in the damaged skin.

[0204]

[0264] Aspect 87: A method for treatment according to any one of the preceding aspects, wherein the step of promoting skin healing further comprises at least a portion of the administered artificial melanin material exerting therapeutic intracellular activity.

[0205]

[0265] Aspect 88: The therapeutic intracellular activity is quenching intracellular free radical species; and / or Adsorbing one or more intracellular inflammatory factors and / or one or more intracellular enzymatic factors. 20. The method for treatment of any one of the preceding aspects, comprising:

[0206]

[0266] Aspect 89: Skin healing is Reduction of the wound area containing damaged tissue; Reduced inflammation of damaged skin; Increased superoxide dismutase activity in damaged skin; Decreased bifold skin thickness of the lesional skin; Reduced swelling of damaged skin; Decreased time to eschar on injured skin; Reduction in the depth of injury to damaged skin; Stabilization of the epithelial layer of damaged skin; A reduction in scar collagen formation in damaged skin; or Any combination of them 20. The method for treatment of any one of the preceding aspects, comprising:

[0207]

[0267] Aspect 90: Skin healing exhibits the following healing properties that are less than the same one or more healing properties in the absence of the artificial melanin material during skin healing: The total time required to reduce the amount or concentration of damaged tissue to 30% of its original amount immediately before administering the melanin preparation; The total time to reduce inflammation in the damaged skin by 40% immediately before administering the melanin preparation; The total time required to reduce the two-fold skin thickness of the lesion to 25% immediately before administering the melanin preparation; The total time required to reduce the edema of the injured skin to 25% of its original value immediately before administering the melanin preparation; The total time required to reduce the depth of injury to 30% of that of the damaged skin immediately before administering the melanin preparation; total time to eschar detachment in the area; Any combination of them 2. The method for treatment of any one of the preceding aspects, characterized by one or more of:

[0208]

[0268] Aspect 91 : Skin healing exhibits the following healing properties that are greater than the same one or more healing properties in the absence of the artificial melanin material during skin healing: the rate of reduction of the wound area, including the damaged skin; Reduced rate of inflammation in damaged skin; The rate of reduction in the bifold skin thickness of the injured skin; The rate of reduction of edema of damaged skin; The rate of decrease in the depth of injury to damaged skin; The rate of stabilization of the epithelial layer of damaged skin; Superoxide dismutase activity in damaged skin; A reduction in scar collagen formation in damaged skin; or Any combination thereof 2. The method for treatment of any one of the preceding aspects, characterized by one or more of:

[0209]

[0269] Aspect 92: A method for treatment according to any one of the preceding aspects, wherein skin healing comprises a 20% to 50% reduction in one or more inflammatory factors and / or one or more enzymatic factors in the damaged skin over 72 hours (in the presence of the functionalized artificial melanin material; over 72 hours of treatment with the formulation).

[0210]

[0270] Aspect 93: Skin healing is A 30-50% reduction in CXCL1 in damaged skin over 72 hours (in the presence of functionalized artificial melanin material; over 72 hours of treatment with the formulation); A 20-30% reduction in MMP3 in damaged skin over 72 hours (in the presence of functionalized artificial melanin material; over 72 hours of treatment with the formulation); A 40% reduction in MMP9 in damaged skin at 72 hours (in the presence of functionalized artificial melanin material; at 72 hours of treatment with the formulation); A 30-40% reduction in Col3a1 in damaged skin at 72 hours (in the presence of functionalized artificial melanin material; at 72 hours of treatment with the formulation); A reduction in one or more proteins associated with the MAPK / ERK pathway in damaged skin over 72 hours (in the presence of functionalized artificial melanin material; after 72 hours of treatment with the formulation); An increase in one or more proteins, including CD31, associated with angiogenesis (blood vessel formation) in damaged skin over 72 hours (in the presence of functionalized artificial melanin material; over 72 hours of treatment with the formulation); A 20-30 reduction in osm, IL-8, CCL20, and / or ICAM1 in injured skin at 72 hours (in the presence of functionalized artificial melanin material; at 72 hours of treatment with the formulation); or any combination thereof 20. The method for treatment of any one of the preceding aspects, comprising:

[0211]

[0271] Embodiment 94: A method for treatment according to any one of the preceding embodiments, wherein the melanin preparation comprises one or more additives.

[0212]

[0272] Aspect 95: A method for treatment according to any one of the preceding aspects, wherein the melanin formulation does not comprise artificial melanin material to which a non-melanin therapeutic agent has been attached or which is functionalized with a non-melanin therapeutic agent.

[0213]

[0273] Aspect 96: A method for treatment according to any one of the preceding aspects, wherein the melanin formulation does not comprise hollow and / or semi-hollow melanin particles carrying a non-melanin therapeutic agent.

[0214]

[0274] Embodiment 97: A method for treatment according to any one of the preceding embodiments, wherein the melanin formulation does not comprise a non-melanin therapeutic agent.

[0215]

[0275] Aspect 98: A method for treatment according to any one of the preceding aspects, wherein the melanin formulation is such that the administering step comprises forming a layer of artificial melanin material on at least a portion of the damaged skin.

[0216]

[0276] Aspect 99: A method for treatment according to any one of the preceding aspects, wherein the administering step occurs after a skin damage event has occurred in the area of ​​the subject.

[0217]

[0277] Embodiment 100: A method for treatment according to any one of the preceding embodiments, comprising a step of damaging the skin prior to the administering step to form damaged skin.

[0218]

[0278] Embodiment 101: A method for treatment according to any one of the preceding embodiments, comprising repeating the administering step.

[0219]

[0279] Embodiment 102: A method for treatment according to any one of the preceding embodiments, wherein the subject is a mammal and / or the skin to be healed is mammalian skin.

[0220]

[0280] Embodiment 103: A method for treatment according to any one of the preceding embodiments, wherein the melanin formulation is characterized as an ointment, cream, gel, paste, or any combination thereof.

[0221]

[0281] Embodiment 104: A method for treatment according to any one of the preceding embodiments, wherein the one or more hydrophobic solvents constitute at least approximately 60%, optionally at least 65%, optionally at least 70%, optionally at least 75%, optionally at least 80%, optionally at least 85%, optionally at least 95%, optionally at least 95% of the total solvent concentration in the formulation.

[0222]

[0282] Aspect 105: A method for treatment according to any one of the preceding aspects, wherein the one or more hydrophobic solvents comprise dichloromethane, chloroform, tetrahydrofuran, toluene, ethyl acetate, hexane, cyclohexane, squalene, squalene, petrolatum, a petrolatum-containing solvent or solvent mixture, a petrolatum ointment, a petrolatum-based ointment, or any combination thereof.

[0223]

[0283] Embodiment 106: A method for treatment according to any one of the preceding embodiments, wherein the one or more hydrophobic solvents comprise petrolatum or petrolatum.

[0224]

[0284] Aspect 107: A method for treatment according to any one of the preceding aspects, wherein the melanin formulation is a sunscreen or sunblock product for application to the skin; and a functionalized artificial melanin material is provided in the formulation to promote skin healing in the event of UV-induced skin damage.

[0225]

[0285] Aspect 108a: The method of treatment of any one of the preceding aspects, wherein the concentration of the functionalized artificial melanin material in the melanin formulation is selected from the range of 0.5 mg / mL to 100 mg / mL, and any ranges and values ​​therebetween are expressly contemplated, inclusively, and disclosed herein. Aspect 108b: The concentration of the functionalized artificial melanin material in the melanin formulation is selected from the range of about 0.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 100 mg / mL, optionally selected from the range of about 1.5 mg / mL to about 100 mg / mL, optionally selected from the range of about 2.0 mg / mL to about 100 mg / mL, optionally selected from the range of about 2.5 mg / mL to about 100 mg / mL, and optionally selected from the range of about 1.0 mg / mL to about 75 mg / mL. 10. The method for treatment of any one of the preceding embodiments, wherein the ribonucleotide concentration is optionally selected from the range of about 1.0 mg / mL to about 50 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 40 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 30 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 20 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 10 mg / mL, optionally selected from the range of about 1.0 mg / mL to about 5 mg / mL.

[0226]

[0286] Embodiment 109a: A method for treatment according to any one of the preceding embodiments, wherein the melanin formulation is characterized by a contact angle of at least approximately 90°, optionally at least approximately 100°, optionally at least approximately 105°, optionally at least approximately 110°, optionally at least approximately 115°, optionally at least approximately 120°, optionally at least approximately 125°, optionally at least approximately 130°, optionally at least approximately 135°, optionally at least approximately 140°, optionally at least approximately 145°, optionally at least approximately 150°, optionally at least approximately 155°, optionally at least approximately 160°. Embodiment 109b: The melanin formulation is selected from the range of approximately 115° to approximately 180°, optionally selected from the range of approximately 120° to approximately 180°, optionally selected from the range of approximately 125° to approximately 180°, optionally selected from the range of approximately 130° to approximately 180°, optionally selected from the range of approximately 135° to approximately 180°, optionally selected from the range of approximately 140° to approximately 180°, optionally selected from the range of approximately 145° to approximately 180°, optionally selected from the range of approximately 150° to approximately 180°, approximately 155° to approximately 180° 160°、170°、180°、190°、200°、210°、220°、230°、240°、250°、260°、270°、280°、290°、300°、315°、320°、335°、340°、350°、360°、370°、415°、420°、430°、445°、450°、460°、470°、480°、500°、515°、520°、535°、540°、550°、560°、570°、580°、600°、615°、625°、635°、640°、650°、760°、770°、800°、815°、825°、900°、915°、925°、930°、940°、950°、960°、970°、980°、990°、1000°、1100°、115°、120°、130°、140°、150°、160°、170°、180°、190°、200°、215°、220°、230°、140°、150°、240°、250°、260°、270°、280°、290°、290°、300°、315°、320°、335°、340°、350°、350°、360°、370°、380°、415°、425°、435°、440°、450°、460°、570°、580

[0227]

[0287] Embodiment 110: A method for treatment according to any one of the preceding embodiments, wherein the dispersed functionalized artificial melanin nanoparticles in the melanin formulation are characterized by a zeta potential of about −40 mV or more, optionally about −35 mV or more, optionally about −30 mV or more, optionally about −25 mV or more, optionally about −20 mV or more, optionally about −15 mV or more, optionally about −10 mV or more, optionally about −5 mV or more, optionally about 5 mV or more, optionally about 10 mV or more, optionally about 15 mV or more, optionally about 20 mV or more.

[0228]

[0288] Embodiment 111: A method for treatment according to any one of the preceding embodiments, wherein the melanin preparation is characterized as a stable colloid.

[0229]

[0289] Embodiment 112: A method for preparing a functionalized artificial melanin material according to any one of the preceding embodiments, comprising: providing non-functionalized artificial melanin nanoparticles; exposing the non-functionalized artificial melanin nanoparticles to a precursor of the modifier for a limited time; wherein the exposing step comprises: Conjugating non-functionalized artificial melanin nanoparticles with a precursor, thereby forming functionalized artificial melanin nanoparticles with a modifier. A method comprising:

[0230]

[0290] Embodiment 113: A method for preparing a functionalized artificial melanin material, comprising: providing non-functionalized artificial melanin nanoparticles; exposing the non-functionalized artificial melanin nanoparticles to a precursor of the modifier for a limited time; wherein the exposing step comprises: Conjugating non-functionalized artificial melanin nanoparticles with a precursor, thereby forming functionalized artificial melanin nanoparticles with a modifier. wherein the functionalized artificial melanin nanoparticles comprise a surface functionalized with a modifier via a linker group; the modifying agent comprises a linker group and a functional group attached to the linker group; The method wherein the linker group is a nucleophilic group.

[0231]

[0291] Embodiment 114: A method for preparing a functionalized artificial melanin material according to any one of the preceding embodiments, wherein the linker group is an amine group, a thiol group, or any combination thereof.

[0232]

[0292] Embodiment 115: A method for preparing a functionalized artificial melanin material according to any one of the preceding embodiments, wherein the linker group is an amine group.

[0233]

[0293] Embodiment 116: A method for preparing a functionalized artificial melanin material according to any one of the preceding embodiments, wherein the non-functionalized artificial melanin nanoparticles are hydrophilic and dispersed in an aqueous solution.

[0234]

[0294] Embodiment 117: A method for preparing a functionalized artificial melanin material described in any one of the preceding embodiments, wherein the exposing step comprises adding a predetermined amount of precursor to an aqueous solution having non-functionalized artificial melanin nanoparticles.

[0235]

[0295] Aspect 118: A method for preparing a functionalized artificial melanin material described in any one of the preceding aspects, wherein the conjugating step includes rendering the functionalized artificial melanin nanoparticles more hydrophobic than the provided non-functionalized artificial melanin nanoparticles.

[0236]

[0296] Aspect 119: A method for preparing a functionalized artificial melanin material according to any one of the preceding aspects, comprising extracting the material or functionalized artificial melanin nanoparticles thereof.

[0237]

[0297] Aspect 120: A method for preparing a functionalized artificial melanin material described in any one of the preceding aspects, comprising a step of aging or oxidizing non-functionalized artificial melanin nanoparticles to form or increase the content of quinones in the non-functionalized artificial melanin nanoparticles.

[0238]

[0298] Aspect 121: A method for preparing a functionalized artificial melanin material according to any one of the preceding aspects, wherein the providing step comprises preparing non-functionalized artificial melanin nanoparticles.

[0239]

[0299] Embodiment 122: A method for preparing a functionalized artificial melanin material according to any one of the preceding embodiments, wherein the conjugating step occurs via a Michael addition or via a Schiff base reaction.

[0240]

[0300] Aspect 123: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the functionalized artificial melanin material or each of the functionalized artificial melanin nanoparticles thereof is not bound to, conjugated to, attached to, coated by, encapsulated by, or otherwise chemically associated with a natural or biological proteinaceous matrix, component, or lipid.

[0241]

[0301] Aspect 124: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein each of the functionalized artificial melanin material or functionalized artificial melanin nanoparticles thereof is characterized as eumelanin, pheomelanin, allomelanin, or a combination thereof.

[0242]

[0302] Aspect 125: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein the functionalized artificial melanin material comprises artificial allomelanin nanoparticles, artificial polydopamine nanoparticles, or any combination thereof.

[0243]

[0303] Aspect 126: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein each of the functionalized artificial melanin materials or functionalized artificial melanin nanoparticles thereof comprises multiple types of melanin oligomers and / or polymers; and each melanin oligomer and / or polymer comprises multiple covalently bonded melanin building blocks.

[0244]

[0304] Aspect 127: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the melanin building blocks comprise one or more substituted or unsubstituted catechol-based monomer units, substituted or unsubstituted polyol-based monomer units, substituted or unsubstituted phenol-based monomer units, substituted or unsubstituted indole-based monomer units, substituted or unsubstituted benzothiazine-based monomer units, substituted or unsubstituted benzothiazole-based monomer units, substituted or unsubstituted dopamine-based monomer units, or any combination thereof.

[0245]

[0305] Embodiment 128: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding embodiments, wherein the functionalized artificial melanin material comprises artificial allomelanin nanoparticles.

[0246]

[0306] Aspect 129: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein the functionalized artificial melanin material comprises solid or non-porous artificial allomelanin nanoparticles, walnut artificial allomelanin nanoparticles, hollow artificial allomelanin nanoparticles, lacy artificial allomelanin nanoparticles, or a combination thereof.

[0247]

[0307] Aspect 130: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein at least a portion of the melanin building blocks each independently comprise a substituted or unsubstituted naphthalene.

[0248]

[0308] Aspect 131: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein at least a portion of the melanin building blocks each independently comprise a dihydroxynaphthalene.

[0249]

[0309] Aspect 132: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein at least a portion of the artificial melanin material comprises nitrogen-free melanin oligomers.

[0250]

[0310] Aspect 133: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein at least a portion of the artificial melanin material comprises polydopamine.

[0251]

[0311] Aspect 134: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein at least a portion of the melanin building blocks each independently comprise a substituted or unsubstituted dopamine monomer.

[0252]

[0312] Aspect 135: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method according to any one of the preceding aspects, wherein at least a portion of the melanin building blocks are each independently selected from the group consisting of substituted or unsubstituted dihydroxydopamine monomer units, substituted or unsubstituted dioxydopamine monomer units, substituted or unsubstituted dihydroxynaphthalene monomer units, substituted or unsubstituted dihydroxyphenylalanine monomer units, substituted or unsubstituted dioxydopamine monomer units, substituted or unsubstituted tyrosine monomer units, substituted or unsubstituted tyramine monomer units, any derivatives thereof, and any combinations thereof.

[0253]

[0313] Aspect 136: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein at least a portion of the melanin basic units are each independently selected from the group consisting of 3,4-dihydroxydopamine monomer units, 3,4-dioxydopamine monomer units, 3,4-dihydroxynaphthalene monomer units, 1,8-dihydroxynapthalene, 1-3,4-dihydroxyphenylalanine monomer units, and any combination thereof.

[0254]

[0314] Aspect 137: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein at least 50% of the plurality of melanin oligomers are selected from the group consisting of monomer units, dimers, trimers, tetramers, pentamers, and any combination thereof.

[0255]

[0315] Aspect 138: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein each melanin oligomer is non-covalently associated with at least one other melanin oligomer or melanin monomer via at least one of hydrogen bonding and π-π stacking of naphthalene rings; and the melanin monomer comprises a melanin basic unit.

[0256]

[0316] Embodiment 139: The artificial melanin material comprises a porous artificial melanin material; the melanin oligomers and / or polymers of the porous artificial melanin material are arranged to form an internal structure having a plurality of pores; and the porous artificial melanin material has a thickness of 0.1 cm 3 10. The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding aspects, characterized by a pore volume per mass of material of 1 / g or more, and at least a portion of the pores having at least one size dimension of 0.5 nm or more.

[0257]

[0317] Aspect 140: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein the artificial melanin material comprises artificial melanin particles; and at least a portion of the artificial melanin particles are solid particles, hollow particles, lacy particles, or any combination thereof.

[0258]

[0318] Aspect 141: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein at least a portion of the artificial melanin material comprises one or more selenomelanine polymers; the one or more selenomelanine polymers comprise a plurality of covalently bonded selenomelanin building blocks; and the chemical formula of each of the one or more selenomelanin building blocks includes at least one selenium atom.

[0259]

[0319] Embodiment 142: The functionalized artificial melanin material, dispersion, melanin-containing formulation, or method of any one of the preceding embodiments, wherein each selenomelanin polymer is a pheomelanin.

[0260]

[0320] Aspect 143: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein the chemical formula of each of the one or more selenomelanin building blocks includes at least one covalent bond with each of the at least one selenium atom.

[0261]

[0321] Aspect 144: A functionalized artificial melanin material, dispersion, melanin-containing formulation, or method described in any one of the preceding aspects, wherein the chemical formula of each of the one or more selenomelanin building blocks comprises substituted or unsubstituted benzoselenazine or a derivative thereof, substituted or unsubstituted benzoselenazole or a derivative thereof, substituted or unsubstituted 7,10-dihydro-2H-[1,4]selenazino[3,2-h]isoquinolin-3(4H)-one or a derivative thereof, substituted or unsubstituted benzoselenazinone or a derivative thereof, or any combination thereof.

[0262]

[0322] Aspect 145: A functionalized artificial melanin material, melanin-containing formulation, dispersion, thin film, or method described in any one of the preceding aspects, wherein the functionalized artificial melanin material described in any one of the preceding aspects is a functionalized form of an artificial melanin material described in any aspect described below or hereafter, as described in one or more aspects herein.

[0263]

[0323] Aspect 146: The functionalized artificial melanin material of any one of the preceding aspects is disclosed in International Patent Application No. PCT / US2017 / 041596 (published as International Patent Publication No. WO2018013609A2), International Patent Application No. PCT / US2020 / 039769 (published as International Patent Publication No. WO2021021350A3), International Patent Application No. PCT / US2020 / 057902 (published as International Patent Publication No. WO2021087076A1), International Patent Application No. PCT / US2020 / 057939 (published as International Patent Publication No. WO2021096692A1), International Patent

[0023] The functionalized artificial melanin material, melanin-containing formulation, dispersion, thin film, or method of any one of the preceding aspects is a functionalized form according to one or more aspects herein of any of the artificial melanin materials described in Application No. International Application No. PCT / US2023 / 012182 (published as International Patent Publication No. WO2023150205A1), International Patent Application No. International Application No. PCT / US2022 / 026669 (published as International Patent Publication No. WO2022232356A1), and / or International Patent Application No. International Application No. PCT / US2021 / 064842 (published as International Patent Publication No. WO2022140532A2).

[0264]

[0324] Aspect 147: A functionalized artificial melanin material, melanin-containing formulation, dispersion, thin film, or method according to any one of the preceding aspects, wherein the functionalized artificial melanin material according to any one of the preceding aspects is an artificial melanin material according to any aspect described below or hereafter, which has been functionalized according to any one or more aspects described herein.

[0265]

[0325] Aspect 148: The functionalized artificial melanin material of any one of the preceding aspects, wherein the functionalized artificial melanin material is functionalized according to any one or more aspects described herein, see International Patent Application No. PCT / US2017 / 041596 (published as International Patent Publication No. WO2018013609A2), International Patent Application No. PCT / US2020 / 039769 (published as International Patent Publication No. WO2021021350A3), International Patent Application No. PCT / US2020 / 057902 (published as International Patent Publication No. WO2021087076A1), International Patent Application No. PCT / US2020 / 057939 (published as International Patent Publication No. WO2021096692A1), International Patent Application No. PCT / US2023 / 012182 (published as International Patent Publication No. WO2023150205A1), International Patent Application No. PCT / US2022 / 026669 (published as International Patent Publication No. WO2022232356A1), and / or International Patent Application No. PCT / US2021 / 064842 (published as International Patent Publication No. WO2022140532A2).

[0266]

[0326] Various potentially useful and optional explanations, background information, applications or uses of embodiments and aspects herein, terminology (to the extent not inconsistent with the terms as defined herein), mechanisms, compositions (such as artificial melanin nanoparticles and compositions and properties thereof), methods, techniques, measurements, calculations, definitions, and other embodiments and aspects are incorporated herein by reference in their entirety to the extent not inconsistent with the present specification, including International Patent Application No. PCT / US2017 / 041596 (published as International Patent Publication No. WO2018013609A2), International Patent Application No. PCT / US2020 / 039769 (published as International Patent Publication No. WO2021021350A3), International Patent Application No. No. PCT / US2020 / 057902 (published as International Patent Publication No. WO2021087076A1), International Patent Application No. PCT / US2020 / 057939 (published as International Patent Publication No. WO2021096692A1), International Patent Application No. PCT / US2023 / 012182 (published as International Patent Publication No. WO2023150205A1), International Patent Application No. PCT / US2022 / 026669 (published as International Patent Publication No. WO2022232356A1), and International Patent Application No. PCT / US2021 / 064842 (published as International Patent Publication No. WO2022140532A2).

[0267]

[0327] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material comprises synthetic melanin particles, also referred to herein as artificial melanin particles, also referred to herein interchangeably as artificial melanin-like particles or synthetic melanin-like particles, prepared by natural oxidation of melanin monomers in aqueous solution under alkaline conditions to produce biocompatible synthetic analogs of naturally occurring melanosomes.

[0268]

[0328] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material includes synthetic melanin particles, including non-naturally occurring particles composed of (e.g., comprising, consisting of, or consisting essentially of) melanin that is not bound to, conjugated to, attached to, coated by, encompassed by, or otherwise associated with lipids (i.e., lipids comprising one or more proteins, such as the lipid (plasma) membrane of a melanocyte or melanosome). Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material includes synthetic melanin particles, including non-naturally occurring particles composed of (e.g., consisting of, or consisting essentially of) melanin that is not bound to, conjugated to, attached to, coated by, encompassed by, or otherwise associated with a proteinaceous lipid (i.e., a lipid that includes one or more proteins, such as the lipid (plasma) membrane of a melanocyte or melanosome).

[0269]

[0329] Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material includes synthetic melanin particles including a melanin polymer that is a fused ring melanin polymer that includes (e.g., consists of, or consists essentially of) fused ring heteroaryl and / or heterocycloalkyl monomer monomers. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material includes synthetic melanin particles including a melanin polymer that is a fused ring metal-bound melanin polymer, including a melanin polymer bound to multiple transition metals, including, but not limited to, iron. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material includes synthetic melanin particles including a fused ring melanin polymer that is a dopamine monomer, including, but not limited to, dihydroxydopamine, 3,4-dihydroxydopamine, dioxidopamine, and / or 3,4-dioxydopamine. Optionally in any one of embodiments 1 through 148, or optionally in any one of the preceding embodiments, each of the fused-ring heteroaryl monomers and / or fused-ring heterocycloalkyl monomers is optionally substituted with one or more substituents selected from hydroxyl, carboxyl, and / or oxy. Optionally in any one of embodiments 1 through 148, or optionally in any one of the preceding embodiments, each of the fused-ring heteroaryl monomers is a 6,6-fused-ring heteroaryl monomer, a 5,6-fused-ring heteroaryl monomer, or a 6,5-fused-ring heteroaryl monomer, and each of the fused-ring heterocycloalkyl moieties is a 6,6-fused-ring heterocycloalkyl monomer, a 5,6-fused-ring heterocycloalkyl monomer, or a 6,5-fused-ring heterocycloalkyl monomer.Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the fused ring heteroaryl and / or fused ring heterocycloalkyl monomers (in monovalent or divalent form) are selected from indole (e.g., dihydroxyindole, 5,6-dihydroxyindole (DHI), 5,6-dihydroxyindole-2-carboxylic acid, dioxindole, 5,6-dioxindole, 5,6-hydroxyindole-2-carboxylic acid), benzothiazine, and benzothiazole. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the fused ring monomer units of the fused ring melanin polymer are dihydroxy fused ring units (e.g., dihydroxy fused ring heteroaryl and / or dihydroxy fused ring heterocycloalkyl monomers) in which hydroxy substituents are bonded to adjacent carbons of a six-membered ring (e.g., a six-membered carbocyclic ring) of the fused ring monomer (also referred to herein as a "catechol fused ring monomer"). Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the fused ring melanin polymer can also include oxidized versions of dihydroxy fused ring units in which one or both of the hydroxyl substituents are oxy substituents. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the synthetic melanin particles can be in the form of spheres, hollow spheres, nanorods, worm-like structures, cylindrical structures, and the like, preferably having a high aspect ratio, with at least one axis thereof being from about 1 nm to about 1000 nm, from about 1 nm to about 1000 nm, from about 50 nm to about 500 nm, or from about 100 nm to about 300 nm. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the synthetic melanin particles are in the form of spheres having an average diameter of about 50 nm to about 500 nm, about 100 nm to about 300 nm, about 150 nm to about 250 nm, or about 250 nm. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the synthetic melanin particles are in the form of hollow spheres, optionally filled with silica.Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the synthetic melanin particles can function as a pigment. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the synthetic melanin particles are synthetic melanin nanoparticles.

[0270]

[0330] Optionally in any one of Aspects 1-148 or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes artificial melanin nanoparticles, wherein each melanin nanoparticle of the plurality of artificial melanin nanoparticles comprises a plurality of melanin oligomers; each melanin oligomer comprises a plurality of covalently bonded melanin building blocks; and each melanin building block comprises a substituted or unsubstituted naphthalene.

[0271]

[0331]

[0013] Optionally in any one of Aspects 1-148 or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin nanoparticle of the plurality of artificial melanin nanoparticles comprises a plurality of melanin oligomers, each melanin oligomer comprising a plurality of covalently bonded melanin building blocks, and the plurality of artificial melanin nanoparticles are characterized by a peak size selected from the range of 100 nm to 300 nm and a polydispersity index selected from 0.10 or less, and optionally for some embodiments, a polydispersity index selected from 0.3 or less and optionally for some embodiments, a polydispersity index selected from 0.2 or less. Optionally, the plurality of artificial melanin nanoparticles are characterized by a peak size selected from the range of 100 nm to 200 nm and a polydispersity index selected from 0.10 or less.

[0272]

[0332] Optionally, in any one of embodiments 1-148, or optionally, in any one of the preceding embodiments, the artificial melanin material disclosed herein includes artificial melanin nanoparticles, wherein each melanin nanoparticle of the plurality of artificial melanin nanoparticles comprises a plurality of melanin oligomers; each melanin oligomer comprises a plurality of covalently bonded melanin building blocks; and the plurality of artificial melanin nanoparticles exhibit structural color. Optionally, the plurality of artificial melanin nanoparticles exhibit structural color when they are in the form of a layer or film, such as a monolayer or thicker, or in the form of pellets, e.g., free-standing pellets. Optionally, the plurality of artificial melanin nanoparticles exhibit structural color when they are in the form of a packed and / or ordered structure. Optionally, the plurality of artificial melanin nanoparticles exhibit structural color when they are dried or otherwise deposited on a substrate.

[0273]

[0333] Optionally in any one of Aspects 1-148 or any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin nanoparticle of a plurality of artificial melanin nanoparticles comprises a plurality of melanin oligomers, each melanin oligomer comprising a plurality of covalently linked melanin building blocks, and at least 50% of the plurality of melanin oligomers are selected from the group consisting of monomers, dimers, trimers, tetramers, pentamers, and any combination thereof, where the monomers, dimers, trimers, tetramers, and pentamers have 1, 2, 3, 4, and 5 melanin building blocks, respectively. Optionally, at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, and optionally at least 80% of the plurality of melanin oligomers are selected from the group consisting of dimers, trimers, tetramers, pentamers, and any combination thereof, and the artificial melanin nanoparticles further comprise a monomer. Optionally, at least 50% of the plurality of melanin oligomers are selected from the group consisting of dimers, trimers, tetramers, pentamers, and any combination thereof, and the artificial melanin nanoparticles further comprise a monomer. Optionally, at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, and optionally at least 80% of the plurality of melanin oligomers are selected from the group consisting of dimers, trimers, tetramers, and any combination thereof, and the artificial melanin nanoparticles further comprise a monomer. Optionally, at least 50% of the plurality of melanin oligomers are selected from the group consisting of dimers, trimers, tetramers, and any combination thereof, and the artificial melanin nanoparticles further comprise monomers.Optionally, at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, and optionally at least 80% by weight of each of the plurality of artificial melanin nanoparticles, or of at least 80% of each, are melanin oligomers selected from the group consisting of monomers (each monomer having only one melanin building block) and / or dimers, trimers, tetramers, pentamers, and any combination thereof. Optionally, at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, and optionally at least 80% by weight of each of the plurality of artificial melanin nanoparticles, or of at least 80% of each, are melanin oligomers selected from the group consisting of monomers (each monomer having only one melanin building block) and dimers, trimers, tetramers, pentamers, and any combination thereof. Optionally, at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, and optionally at least 80% by weight of each of the plurality of artificial melanin nanoparticles, or of at least 80% of each, are melanin oligomers selected from the group consisting of monomers (each monomer having only one melanin building block) and / or dimers, trimers, tetramers, and any combination thereof. Optionally, at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, and optionally at least 80% by weight of each of the plurality of artificial melanin nanoparticles, or of at least 80% of each, are melanin oligomers selected from the group consisting of monomers (each monomer having only one melanin building block) and dimers, trimers, tetramers, and any combination thereof.

[0274]

[0334] Optionally in any one of Aspects 1-148 or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin nanoparticle of the plurality of artificial melanin nanoparticles comprises a plurality of melanin oligomers; each melanin oligomer comprises a plurality of covalently bonded melanin building blocks; and each nanoparticle has a sphericity of less than 0.90 and a shape characterized as at least one of a walnut-like, a collapsed sphere or collapsed ellipsoid, and a sphere or ellipsoid with multiple dimples.

[0275]

[0335]

[0013] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin nanoparticle of the plurality of artificial melanin nanoparticles comprises a plurality of melanin oligomers, each melanin oligomer comprising a plurality of covalently bonded melanin building blocks, and wherein the plurality of artificial melanin nanoparticles are characterized by a radical scavenging activity that is greater than the radical scavenging activity of polydopamine nanoparticles having the same diameter as the plurality of artificial melanin nanoparticles under otherwise identical conditions. Optionally, the plurality of artificial melanin nanoparticles are characterized by a radical scavenging activity that is at least 5%, optionally at least 10%, optionally at least 15%, and optionally at least 20% greater than the radical scavenging activity of polydopamine nanoparticles having the same diameter as the plurality of artificial melanin nanoparticles under otherwise identical conditions.

[0276]

[0336] Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin building block comprises a substituted or unsubstituted naphthalene. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin building block comprises a dihydroxynaphthalene. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin building block comprises 1,8-dihydroxynaphthalene. According to certain embodiments, each melanin building block has the formula FX100: [ka] The structure includes:

[0277]

[0337]

[0013] Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin oligomer does not contain nitrogen. According to certain embodiments, at least 20%, optionally at least 40%, optionally at least 50%, and optionally at least 80% of the plurality of melanin oligomers are dimers having two covalently linked melanin building blocks. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein 20%-80% of the plurality of melanin oligomers are dimers having two covalently linked melanin building blocks.

[0013] Optionally in any one of Aspects 1-148 or any one of the preceding aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein at least 50% of the plurality of melanin oligomers are selected from the group consisting of monomers, dimers, trimers, tetramers, pentamers, and any combination thereof. The monomers, dimers, trimers, tetramers, and pentamers have 1, 2, 3, 4, and 5 melanin building blocks, respectively. Optionally, at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, and optionally at least 80% of the plurality of melanin oligomers are selected from the group consisting of dimers, trimers, tetramers, pentamers, and any combination thereof, and the artificial melanin nanoparticles further comprise a monomer.

[0023] Optionally in any one of Aspects 1-148 or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein at least 40% of the plurality of melanin oligomers are selected from the group consisting of monomers, dimers, trimers, tetramers, pentamers, and any combination thereof.

[0013] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein at least 20%, optionally at least 40%, and optionally at least 80% of the plurality of melanin oligomers are selected from the group consisting of monomers, dimers, and trimers, and any combination thereof.

[0014] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein at least 50% of the plurality of melanin oligomers are selected from the group consisting of monomers, dimers, and trimers, and any combination thereof.

[0023] Optionally in any one of Aspects 1-148 or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein includes artificial melanin nanoparticles, wherein at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 80%, by weight of each of the plurality of artificial melanin nanoparticles, or at least 80% of each of the plurality of artificial melanin nanoparticles, are melanin oligomers selected from the group consisting of monomers (each monomer having only one melanin base unit) and / or dimers, trimers, tetramers, pentamers, and any combination thereof.

[0023] Optionally in any one of Aspects 1-148 or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein includes artificial melanin nanoparticles, wherein at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 80%, by weight of each of the plurality of artificial melanin nanoparticles, or at least 80% of each of the plurality of artificial melanin nanoparticles, are melanin oligomers selected from the group consisting of monomers (each monomer having only one melanin base unit) and dimers, trimers, tetramers, pentamers, and any combination thereof.

[0023] Optionally in any one of Aspects 1-148 or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein includes artificial melanin nanoparticles, wherein at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 80%, by weight of each of the plurality of artificial melanin nanoparticles, or at least 80% of each of the plurality of artificial melanin nanoparticles, are melanin oligomers selected from the group consisting of monomers (each monomer having only one melanin base unit) and / or dimers, trimers, tetramers, and any combination thereof.

[0013] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, or optionally at least 80%, by weight of each of, or at least 80% of, a plurality of artificial melanin nanoparticles are melanin oligomers selected from the group consisting of monomers (each monomer having only one melanin base unit) and dimers, trimers, tetramers, and any combination thereof.

[0014] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin oligomer is noncovalently associated with at least one other melanin oligomer via at least one of hydrogen bonding and π-π stacking of naphthalene rings.

[0023] Optionally in any one of Aspects 1-148 or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein each melanin oligomer is non-covalently associated with at least one other melanin oligomer or melanin monomer via at least one of hydrogen bonding and π-π stacking of naphthalene rings.Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein the melanin monomer comprises a melanin building block.

[0278]

[0338]

[0013] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein at least 50%, optionally at least 75%, optionally at least 90%, optionally at least 95% of the plurality of nanoparticles are characterized by a sphericity greater than 0.90.

[0014] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein the plurality of nanoparticles are characterized by a polydispersity index of 0.10 or less.

[0013] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, each nanoparticle having a size characteristic, such as a diameter, selected from the range of 10 nm to 1000 nm or less, optionally 100±50 nm to 300±50 nm.

[0014] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, each nanoparticle having a size characteristic, such as a diameter, selected from the range of 10 nm to 1000 nm or less, optionally 20 nm to 500 nm, optionally 100 nm to 900 nm, optionally 200 nm to 900 nm, optionally 100 nm to 800 nm, optionally greater than 250 nm and less than 1000 nm. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein at least 55% (optionally at least 75%, optionally at least 80%, optionally at least 85%) of the nanoparticles each have a size characteristic, such as a diameter, selected from the range of greater than 200 nm, optionally greater than 250 nm to less than 1000 nm.

[0013] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, each nanoparticle having a size characteristic, such as a diameter, selected from the range of 10 nm to 1000 nm or less, optionally 100 nm to 300 nm.

[0014] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, each nanoparticle having a size characteristic, such as a diameter, selected from the range of 20 nm to 300±50 nm.

[0013] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein the plurality of artificial melanin nanoparticles are characterized by a peak size selected from the range of 10 nm to 1000 nm or less, optionally 100 nm to 300 nm.

[0014] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein the plurality of artificial melanin nanoparticles are characterized by a peak size selected from the range of 10 nm to 1000 nm or less, optionally 100 nm to 200 nm.

[0023] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises artificial melanin nanoparticles, wherein the plurality of artificial melanin nanoparticles are characterized by a peak size selected from the range of 50 nm to 300 nm, optionally 50 nm to 200 nm.

[0279]

[0339] Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material in the melanin formulation disclosed herein comprises artificial melanin nanoparticles, wherein the melanin formulation comprises a solvent or solvent mixture that is at least 50% water, optionally at least 75% water, optionally at least 90% water, or optionally at least 95% water by volume. According to certain embodiments, the solvent or solvent mixture comprises an organic solvent. According to certain embodiments, the solvent or solvent mixture comprises a buffer. According to certain embodiments, the organic solvent comprises methanol, ethanol, acetonitrile, acetone dichloromethane, dimethylformamide, ethyl acetate, acetone, or any combination thereof. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin nanoparticles are further aged or further oxidized after synthesis. Optionally, in any one of aspects 1-148, or optionally, in any one of the preceding aspects, aging or further oxidation of the nanoparticles affects their solubility or dispersibility (in the melanin formulation) to increase their stability in the presence of organic solvents. According to certain embodiments, the nanoparticles in the melanin formulation are characterized by a zeta potential or average zeta potential selected from the range of -50 mV to -10 mV, optionally -40 to -20 mV, in a solvent or solvent solution that is optionally at least 95% water by volume. According to certain embodiments, the nanoparticles in the melanin formulation are stably dispersed without forming precipitate after at least 5 hours at a concentration selected from the range of 0.01 mg / mL to 5 mg / mL, optionally 0.01 mg / mL to 1 mg / mL, optionally within 20% of 0.1 mg / mL. According to certain embodiments, the nanoparticles in the melanin formulation are stably dispersed without forming precipitates after at least 12 hours at a concentration selected from the range of 0.01 mg / mL to 5 mg / mL, optionally 0.01 mg / mL to 1 mg / mL, optionally within 20% of 0.1 mg / mL.

[0280]

[0340] Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises melanin monomers, each having a substituted or unsubstituted naphthalene. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises melanin monomers, each having a dihydroxynaphthalene. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises melanin monomers, each having 1,8-dihydroxynaphthalene. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises melanin monomers, each having a nitrogen-free melanin monomer. According to certain embodiments, the artificial melanin material is not derived or extracted from a biological source or living organism.

[0281]

[0341] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein, or the plurality of artificial melanin nanoparticles thereof, is characterized by a radical scavenging activity that is greater than the radical scavenging activity of a polydopamine nanoparticle having the same diameter as the plurality of artificial melanin nanoparticles under otherwise identical conditions. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein, or the plurality of artificial melanin nanoparticles thereof, is characterized by a radical scavenging activity that is at least 10%, optionally at least 15%, and optionally at least 50% greater than the radical scavenging activity of a polydopamine nanoparticle having the same diameter as the plurality of artificial melanin nanoparticles under otherwise identical conditions. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material or plurality of artificial melanin nanoparticles disclosed herein is characterized by a radical scavenging activity of at least 0.012 mol / g using the 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH) assay.

[0282]

[0342]

[0023] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin materials disclosed herein include one or more porous artificial melanin materials. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin materials disclosed herein include (i) a porous artificial melanin material comprising one or more melanin oligomers, polymers, or combinations thereof, wherein the one or more melanin oligomers and / or polymers comprise a plurality of covalently bonded melanin building blocks; and the melanin oligomers and / or polymers are arranged to form an internal structure having a plurality of pores.

[0023] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes: (i) a porous artificial melanin material comprising one or more melanin oligomers, polymers, or combinations thereof, wherein the one or more melanin oligomers and / or polymers comprise a plurality of covalently bonded melanin building blocks; the melanin oligomers and / or polymers are arranged to form an internal structure having a plurality of pores; and the porous artificial melanin material is sized to have a diameter of 0.1 cm or less. 3 / g or more, optional 0.3cm 3

[00130] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises a porous artificial melanin material characterized by a pore volume per mass of material of 0.1 cm or more, wherein at least some of the pores have at least one size dimension, such as a cross-sectional dimension or a longitudinal dimension, of 0.5 nm or more. 3 / g~0.6cm 3 / g, and optionally 0.1 to 1 cm 3 / g, and optionally 0.3 cm 3 / g~0.6cm 3 / g。 Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein includes a porous artificial melanin material that is a microporous material or a mesoporous material. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein includes a porous artificial melanin material, wherein the pores of the porous artificial melanin material comprise micropores having at least one average size dimension, such as a cross-sectional dimension and / or a longitudinal dimension, respectively, selected from the ranges of 0.5 nm to 2.5 nm, and optionally 0.5 nm to 1.3 nm.

[0013] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material, wherein the pores of the porous artificial melanin material comprise mesopores, each having at least one average size dimension, such as a cross-sectional dimension and / or a longitudinal dimension, selected from the ranges of 2 nm to 50 nm, and optionally 2 nm to 25 nm. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material, wherein the pores are characterized by a pore size distribution ranging from 0.5 nm to 50 nm. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material, wherein the pores in the internal structure are formed by the organization of melanin oligomers and / or polymers in the porous artificial melanin material. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material in which the pores in the internal structure are formed by close packing and / or self-assembly of melanin oligomers and / or polymers of the porous artificial melanin material.

[0013] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin materials disclosed herein include porous artificial melanin materials in which the pores in the internal structure are formed by templating melanin oligomers and / or polymers in the porous artificial melanin material. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin materials disclosed herein include porous artificial melanin materials in which the pores are not uniformly distributed throughout the porous melanin material, for example, because the material is non-crystalline and / or amorphous. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin materials disclosed herein include porous artificial melanin materials that are at least partially non-crystalline and / or amorphous.

[0013] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material in which the pores in its internal structure are randomly distributed. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material in which the pores in its internal structure are arranged in a repeating structure, and the amorphous porous artificial melanin material is arranged in an at least partially non-crystalline or amorphous state. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material in which the pores of the porous artificial melanin material comprise one or more pore types selected from the group consisting of cylindrical pores, channel-like pores, slit-shaped pores, ink bottle pores, and any combination thereof.

[0283]

[0343]

[0013] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material having porous melanin particles, such as nanoparticles. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material having porous melanin particles characterized by an average size selected from the range of 20 nm to 500 nm in diameter. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material having porous melanin particles that are one or more of solid particles, hollow particles, lacy particles, and any combination thereof. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin materials disclosed herein include porous artificial melanin materials having solid porous artificial melanin particles, e.g., having pores distributed throughout the particle, e.g., uniformly or randomly distributed, and having no hollow configuration. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin materials disclosed herein include porous artificial melanin materials having lacy porous artificial melanin particles, e.g., having pores distributed throughout the particle, e.g., uniformly or randomly distributed, and having no hollow configuration. Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin materials disclosed herein include porous artificial melanin materials having hollow porous artificial melanin particles.

[0284]

[0344] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding Aspects, the artificial melanin material disclosed herein comprises a porous artificial melanin material having purified or isolated porous melanin particles.

[0285]

[0345]

[0023] Optionally in any one of Aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein includes a porous artificial melanin material having melanin building blocks that are one or more substituted or unsubstituted catechol-based monomers, substituted or unsubstituted polyol-based monomers, substituted or unsubstituted phenol-based monomers, substituted or unsubstituted indole-based monomers, substituted or unsubstituted benzothiazine-based monomers, substituted or unsubstituted benzothiazole-based monomers, substituted or unsubstituted dopamine-based monomers, or any combination thereof.

[0286]

[0346] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein includes a porous artificial melanin material having or being an allomelanin. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, e.g., at least a portion, and optionally all, of the melanin building blocks each independently comprise substituted or unsubstituted naphthalene. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, e.g., at least a portion, and optionally all, of the melanin building blocks each independently comprise dihydroxynaphthalene. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, e.g., at least a portion, and optionally all, of the melanin building blocks each independently comprise 1,8-dihydroxynaphthalene. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, for example, at least a portion, and optionally all, of the melanin building blocks are each independently represented by the formula FX100: [ka] Optionally in any one of embodiments 1-148 or optionally in any one of the preceding embodiments, for example, each melanin oligomer does not include nitrogen.

[0287]

[0347] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises a porous artificial melanin material having polydopamine. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, for example, at least a portion, and optionally all, of the melanin building blocks each independently comprise substituted or unsubstituted dopamine monomers. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, for example, at least a portion, and optionally all, of the melanin building blocks each independently comprise substituted or unsubstituted dopamine monomers. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, for example, at least a portion, and optionally all, of the melanin building blocks each independently comprise substituted or unsubstituted dihydroxydopamine monomers, substituted or unsubstituted dioxydopamine monomers, substituted or unsubstituted dihydroxynaphthalene monomers, substituted or unsubstituted dioxydopamine monomers, and any combination thereof. Optionally in any one of embodiments 1-148, or optionally in any preceding embodiment, for example, at least some, and optionally all, of the melanin building blocks are each independently selected from the group consisting of 3,4-dihydroxydopamine monomers, 3,4-dioxydopamine monomers, 3,4-dihydroxynaphthalene monomers, and any combination thereof.

[0288]

[0348] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises a porous artificial melanin material having allomelanin.

[0289]

[0349]

[0013] Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises a substituted or unsubstituted catechol-based or polyol-based compound. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises a substituted or unsubstituted dopamine monomer. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises a substituted or unsubstituted dopamine monomer, 1,8-dihydroxynaphthalene or a derivative thereof, tyrosine monomer, tyramine monomer, amino acid, phenolamine, catecholamine, or any combination thereof.

[0013] Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein includes a substituted or unsubstituted dopamine monomer, a tyrosine monomer, a tyramine monomer, or a combination thereof. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein does not include a phenol derivative, resorcinol, and / or paraphenylenediamine. Optionally, the dopamine monomer is selected from the group consisting of a substituted or unsubstituted dihydroxydopamine monomer, a dihydroxydopamine dimer, a dihydroxydopamine oligomer, a dioxydopamine monomer, a dioxydopamine dimer, a dioxydopamine oligomer, a dihydroxynaphthalene monomer, a dihydroxynaphthalene dimer, a dihydroxynaphthalene oligomer, a dioxydopamine monomer, a dioxydopamine dimer, a dioxydopamine oligomer, and any combination thereof. Optionally, the dopamine monomer is selected from the group consisting of tyrosine and derivatives, phenol and derivatives, resorcinol and derivatives, and any combination thereof. Optionally, the dopamine monomer is selected from the group consisting of phenol, resorcinol, L-DOPA, tyrosine, and any combination thereof.Optionally, the dopamine monomer is selected from the group consisting of a cysteine ​​derivative, a chalcogenide derivative, selenocysteine, and any combination thereof. Optionally, in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises: [ka] Optionally in any one of embodiments 1 through 148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein comprises one or more monomers selected from the group consisting of: [ka] (In the formula, R 1 ~R 7 one or more (optionally one, optionally two) of R 1 ~R 7 and each other of which is a functional group. 1 ~R 7 The others are hydrogen, C1 to C 10 Alkyl, C3-C 10 Cycloalkyl, C5-C 10 Aryl, C5-C 10 Heteroaryl, C1-C 10 Acyl, C1-C 10 Hydroxyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C5-C 10 Alkylaryl, -CO2R 30 , -CONR 31 R 32 , -COR 33 , -NR 39 R 40 , -NR 41 COR 42 , C1~C10 is selected from the group consisting of alkyl halide, acrylate, or catechol; 30 ~R 42 Each of the groups independently represents hydrogen, C1 to C 10 Alkyl or C5-C 10 Optionally, for any method disclosed herein, the artificial melanin precursor has the formula (FX103): [ka] (In the formula, R 1 ~R 8 one or more (optionally one, optionally two) of R 1 ~R 8 and each other of R is a functional group. 1 ~R 7 The others are hydrogen, C1 to C 10 Alkyl, C3-C 10 Cycloalkyl, C5-C 10 Aryl, C5-C 10 Heteroaryl, C1-C 10 Acyl, C1-C 10 Hydroxyl, C1-C 10 Alkoxy, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C5-C 10 Alkylaryl, -CO2R 30 , -CONR 31 R 32 , -COR 33 , -NR 39 R 40 , -NR 41 COR 42 , C1~C 10 is selected from the group consisting of alkyl halide, acrylate, or catechol; 30 ~R 42 Each of the groups independently represents hydrogen, C1 to C 10 Alkyl or C5-C 10aryl. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises one or more thiol-reactive moieties. Optionally, the thiol-reactive moieties are one or more groups selected from the group consisting of thiol, maleimide, pyridyl disulfide-based compounds, alkene, alkyl halide, and any combination thereof. Optionally in any one of aspects 1-148, or optionally in any one of the preceding aspects, the artificial melanin material disclosed herein comprises one or more monomers having the formula (FX102) or (FX103), where R 1 ~R 8 One or more of is a thiol-reactive moiety such as a thiol, maleimide, pyridyl disulfide-based compound, alkene, alkyl halide, and any combination thereof.

[0290]

[0350] Optionally, in any one of embodiments 1-148, or optionally, in any one of the preceding embodiments, the artificial melanin material disclosed herein includes one or more artificial selenomelanin materials having one or more selenomelanin polymers, wherein the one or more selenomelanin polymers comprise a plurality of covalently bonded selenomelanin building blocks; and the chemical formula of each of the one or more selenomelanin building blocks comprises at least one selenium atom. Optionally, each selenomelanin polymer is a pheomelanin. Optionally, each of the selenomelanin monomers is an amino acid. Optionally, the chemical formula of each of the one or more selenomelanin building blocks comprises at least one covalent bond to each of the at least one selenium atom. Optionally, each of the one or more selenomelanin polymers is not bound to, conjugated to, attached to, coated by, encompassed by, or otherwise chemically associated with a natural or biological proteinaceous matrix, component, or lipid. Optionally, each of the plurality of selenomelanin building blocks is not bound to, conjugated to, attached to, coated by, encompassed by, or otherwise chemically associated with a natural or biological proteinaceous matrix, component, or lipid. Optionally, the chemical formula of each of the one or more selenomelanin building blocks includes one selenium atom and two covalent bonds to the selenium atom. Optionally, the chemical formula of each of the one or more selenomelanin building blocks includes substituted or unsubstituted benzoselenazine or a derivative thereof, substituted or unsubstituted benzoselenazole or a derivative thereof, substituted or unsubstituted 7,10-dihydro-2H-[1,4]selenazino[3,2-h]isoquinolin-3(4H)-one or a derivative thereof, substituted or unsubstituted benzoselenazinone or a derivative thereof, or any combination thereof.Optionally, each of the one or more selenomelanin building blocks comprises a moiety characterized by the formula FX111, FX112, FX113A, FX113B, FX114, any combination thereof, or a derivative of any of these: [ka] Optionally, each of the one or more selenomelanin building blocks comprises a moiety characterized by the formula FX111, FX112, FX113A, FX113B, FX114, or any combination thereof. Optionally, each of the one or more selenomelanin building blocks comprises a moiety characterized by the formula FX111, FX112, FX113A, FX113B, FX114, or any combination thereof. Optionally, each of the one or more selenomelanin building blocks comprises a moiety characterized by the formula FX111, FX112, FX113A, FX113B, or FX114. Optionally, each of the one or more selenomelanin building blocks comprises a moiety characterized by the formula FX111. Optionally, the artificial selenomelanine material is one or more of an artificial selenomelanine nanoparticle, an artificial selenomelanine layer, or an artificial selenomelanine thin film. Optionally, the artificial selenomelanine material is one or more of an artificial selenomelanine nanoparticle. Optionally, each of the one or more selenomelanine building blocks includes a heterocyclic moiety that includes Se as a member of its ring structure. Optionally, each of the one or more selenomelanine building blocks includes a heterocyclic moiety that includes Se and N as members of its ring structure. Optionally, each of the one or more selenomelanine building blocks includes a moiety characterized by the formula FX123, FX124, FX125, FX126, FX127, a derivative of any one of these, or any combination thereof: [ka] Optionally, each of the one or more selenomelanine building blocks comprises a moiety characterized by the formula FX123, FX124, FX125, FX126, FX127, or any combination thereof. Optionally, each of the one or more selenomelanine building blocks comprises a moiety characterized by the formula FX123, FX124, FX125, FX126, or FX127. Optionally, each of the selenomelanine monomers is characterized by the formula FX115, FX116, FX117, FX118, FX119, FX120, or FX121: [ka]

[0291]

[0351] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein includes one or more artificial selenomelanin materials, wherein each of the one or more selenomelanin polymers is not bound to, conjugated to, attached to, coated by, encapsulated by, or otherwise chemically associated with a natural or biological proteinaceous matrix, component, or lipid.

[0292]

[0352] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein includes one or more artificial selenomelanin materials, wherein the chemical formula of each of the one or more selenomelanin building blocks includes benzoselenazine, and the material includes a concentration of benzoselenazine selected from the range of 10 wt.% to 100 wt.%. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material disclosed herein includes one or more artificial selenomelanin materials having a concentration of benzoselenazine selected from the range of 50 wt.% to 60 wt.%. For example, the chemical formula of each of the one or more selenomelanin building blocks includes benzoselenazine, and the material includes a concentration of 55 wt.% benzoselenazine.

[0023] Optionally in any one of embodiments 1-148, or any preceding embodiment, the artificial melanin material disclosed herein includes one or more artificial selenomelanin materials characterized by a selenium concentration selected from the range of 2 wt.% to 23 wt.%. For example, the artificial selenomelanin material can be characterized by a selenium concentration of 12 wt.%.

[0293]

[0353]

[0013] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials, wherein the solvent or solvent mixture is at least 50% water. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles characterized by an absolute value of a zeta potential selected from the range of 15 mV to 50 mV, preferably 20 mV to 50 mV, optionally 15 mV to 40 mV, optionally 20 mV to 40 mV, optionally 15 mV to 30 mV, optionally 20 mV to 30 mV, and optionally 17 mV to 34 mV. (The absolute value, or modulus, of a real number is a real, non-negative value, regardless of its sign.) Optionally, the sign of the zeta potential corresponding to the artificial selenomelanin nanoparticles in the artificial selenomelanin nanoparticle dispersion is negative. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein has a zeta potential of 0.1 mg / mL to 10, relative to the average size of nanoparticles at a 0.1 mg / mL concentration. -4Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles that are size-stable at a nanoparticle concentration selected from the range of 100 mg / mL. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles that are size-stable in a dispersion having a pH of 11, preferably a pH of at least 11, relative to the average size of the nanoparticles in the dispersion having a pH of 7. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles that are size-stable when exposed to a NaCl concentration in the dispersion selected from the range of 50 mM to 250 mM, preferably a NaCl concentration of 250 mM, relative to the average size of the nanoparticles in an equivalent dispersion without NaCl. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles that are stably dispersed in the dispersion under ambient conditions for at least 7 days, preferably at least 14 days, and preferably at least 60 days.

[0294]

[0354] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles characterized by a melanin purity of at least 20%, optionally at least 25%, optionally at least 30%, preferably at least 50%, more preferably at least 70%, even more preferably at least 80%, yet even more preferably at least 90%, more preferably at least 95% for some applications, even more preferably at least 99% for some applications, and yet even more preferably at least 99.9% for some applications.

[0023] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials with artificial selenomelanin nanoparticles, wherein at least 50%, optionally at least 75%, preferably at least 90%, more preferably at least 95%, and even more preferably at least 99% of the plurality of artificial melanin nanoparticles each comprise a selenomelanin polymer having a selenomelanin building block that includes a moiety characterized by the formula FX111, FX112, FX113A, FX113B, FX114, or any combination thereof: [ka] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles, wherein at least 50%, optionally at least 75%, preferably at least 90%, more preferably at least 95%, and even more preferably at least 99% of the plurality of artificial melanin nanoparticles each comprise a selenomelanin polymer having a selenomelanin building block that includes a heterocyclic moiety that includes Se as a member of its ring structure. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles, wherein at least 50%, optionally at least 75%, preferably at least 90%, more preferably at least 95%, and even more preferably at least 99% of the plurality of artificial melanin nanoparticles each comprise a selenomelanin polymer having a selenomelanin building block that includes a heterocyclic moiety that includes Se and N as members of its ring structure. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles, wherein at least 50%, optionally at least 75%, preferably at least 90%, more preferably at least 95%, and even more preferably at least 99% of the plurality of artificial melanin nanoparticles each comprise a selenomelanin polymer having a selenomelanin building block comprising a moiety characterized by the formula FX123, FX124, FX125, FX126, FX127, a derivative of any one of these, or any combination thereof.Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles, wherein at least 50%, optionally at least 75%, preferably at least 90%, more preferably at least 95%, and even more preferably at least 99% of the plurality of artificial melanin nanoparticles each comprise a selenomelanin polymer having a selenomelanin building block that includes a moiety characterized by the formula FX123, FX124, FX125, FX126, FX127, or any combination thereof. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles, wherein at least 50%, optionally at least 75%, preferably at least 90%, more preferably at least 95%, and even more preferably at least 99% of the plurality of artificial melanin nanoparticles each comprise a selenomelanin polymer having a selenomelanin building block that includes a moiety characterized by the formula FX123, FX124, FX125, FX126, or FX127. Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulation disclosed herein comprises one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles, each of the one or more selenomelanin nanoparticles not bound to, conjugated to, attached to, coated by, encapsulated by, or otherwise chemically associated with a natural or biological proteinaceous matrix, component, or lipid.

[0023] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulations disclosed herein comprises one or more artificial selenomelanin materials, wherein at least 50%, optionally at least 75%, preferably at least 80%, preferably at least 90%, more preferably at least 95%, and even more preferably at least 99% of the artificial selenomelanin nanoparticles are each free of artificial melanin monomers.

[0024] Optionally in any one of embodiments 1-148, or optionally in any one of the preceding embodiments, the artificial melanin material in the melanin formulations disclosed herein comprises one or more artificial selenomelanin materials, wherein each of the artificial selenomelanin nanoparticles is free of artificial melanin monomers. For example, an artificial selenomelanin material, such as nanoparticles, may be washed extensively with an HCl solution (e.g., once) and purified water (e.g., three times), such that the artificial selenomelanin material, or a dispersion or formulation thereof, is free of artificial selenomelanin monomers, as characterized by solid-state NMR, UV-Vis spectroscopy, or the like. Optionally, the melanin formulations disclosed herein include melanin monomers at a concentration below the IC50 of each monomer. Optionally, in any one of embodiments 1-148, or optionally, in any one of the preceding embodiments, the artificial melanin material in the melanin formulations disclosed herein includes one or more artificial selenomelanin materials having artificial selenomelanin nanoparticles, each of which is outside (extracellular) of a biological cell.

[0295]

[0355] The present invention can be further understood from the following non-limiting examples.

[0296]

[0356] Example 1: Hydrophobic synthetic melanin nanoparticles:

[0357] Melanin is a natural pigment found in skin and hair that plays a key role in UV radiation protection through its absorption of incident radiation and radical scavenging activity. Synthetic melanins, obtained via oxidative polymerization of inexpensive monomers, successfully replicate these properties and avoid the yield and purity issues associated with natural extraction. The resulting materials are hydrophilic, which limits their applications outside of aqueous systems. Here, we disclose a simple post-synthetic modification (or functionalization) strategy that alters the hydrophobicity of particles via reaction with primary alkylamines. The resulting particles exhibit good long-term stability in organic solvents, expanding their applications to self-assembly and additional biological applications.

[0297]

[0358] Synthetic melanin particles are obtained by oxidative polymerization of 1,8-dihydroxynaphthalene for allomelanin (AMNP) and dopamine for polydopamine (PDA), respectively. Once the particles are collected, they are dispersed in ethanol and reacted with primary alkylamine overnight under constant stirring. The resulting hydrophobic particles (hAMNP and hPDA) are washed with ethanol, and their morphology is confirmed by transmission electron microscopy (TEM) (Figures 23A-23B).

[0298]

[0359] Analysis of the particles revealed an increase in particle diameter after modification, maintained a negative zeta potential after modification, and exhibited good colloidal stability in ethanol (Table 3). Fourier transform infrared (FTIR) spectra of all particles were measured before modification and as KBr pellets (Figures 24A-B). Compared to the original particles, the spectrum of the synthetically modified melanin particles contains two additional peaks at 2920 cm-1 and 2850 cm-1. These correspond to alkane C-H bond stretching and indicate the attachment of alkylamines to the surface of the particles.

[0299]

[0360] Because the original AMNPs are nitrogen-free, it is possible to further confirm the surface modification using X-ray photoelectron spectroscopy (XPS) (Figure 3B). While the original AMNP particles have no nitrogen signal, surface modification results in a significant N signal. Additional analysis by scanning transmission electron microscopy-energy dispersive X-ray (STEM-EDX) further demonstrates an even distribution of alkylamines throughout the particles (Figure 15).

[0300]

[0361] To confirm the hydrophobicity, contact angles of the particles were obtained. A coating of the synthetic melanin was prepared by drop-casting the solution onto a silica chip. Water contact angles were then obtained. The pristine particles have hydrophilic water contact angles of 41.9 ± 0.2° and 46.35 ± 0.06° for AMNP and PDA, respectively. Upon surface functionalization, the water contact angles increase to 130.0 ± 0.8° and 135 ± 4° for AMNP-C18 and PDA-C18, respectively (Table 4).

[0301]

[0362] Chemical surface modification may affect the scavenging activity of synthetic melanin, and therefore, it was assayed in vitro using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. DPPH is a storage-stable radical that is purple in solution and turns yellow upon radical quenching, as monitored at 516 nm. 50 μg of AMNPs scavenged 60% of the radicals, while the same amount of hAMNPs scavenged 40% of the free radicals (Figure 25A). Similarly, 50 μg of PDA scavenged 60% of the radicals, while the same amount of PDA-C18 scavenged 50% of the free radicals (Figure 25B). While this is a decrease compared to the original particles, radical scavenging activity is still maintained.

[0302]

[0363] To explore the expanded applications of hydrophobic melanin, AMNPs were successfully assembled into different films. Silicon substrates were prepared by submerging the silicon at the bottom of a Milli-Q water bath. AMNP-C18 was dispersed in 1-butanol, and the colloidal suspension was added dropwise to the water surface, resulting in the formation of a continuous, close-packed monolayer film. The silicon substrate was then lifted out of the solution, resulting in a thin film. This process was repeated, adding one layer at a time, to prepare bilayer and trilayer films (Figures 4A-G). This protocol was applied to other AMNPs with different morphologies that could also assemble into thin films.

[0303]

[0364] The solubility of hydrophobic particles was qualitatively assayed in commercially available vehicles: petrolatum, Aquaphor, squalene, and squalane. Petrolatum and Aquaphor are petrolatum-based ointments that have been used in clinics for dermal application in wound healing. These vehicles were chosen for their clinical and biological relevance. The solubility of synthetic melanin particles was assayed in these compounds by vigorous mixing. Both hydrophobic particles, AMNP-C18 and PDA-C18, qualitatively exhibit better solubility in various excipients compared to the original particles, as evidenced by the observation of fewer microparticles in the suspension and the even distribution of the hydrophobic particles by color (Figure 26). The solubility of the original particles in Aquaphor can be attributed to the addition of hydrophilic glycerin to petrolatum, which makes Aquaphor more non-hydrophobic overall compared to the other vehicles. In petrolatum, AMNP and PDA do not incorporate into the ointment, as evidenced by the dark microparticles surrounded by the clear ointment. In the case of squalene and squalane, PDA-C18 is found to be better incorporated, with a more uniform brown color of the solution and fewer microparticles, while squalane and squalene cause the PDA particles to settle to the bottom of the glass substrate (Figures 27A-B).

[0304]

[0365] Potential applications of the technology include surface assembly of synthetic melanin films, topical dermal application, skin tanning, and improved wound healing by reducing inflammation.

[0305]

[0366] Advantages of this technique compared to other solutions include its scalability, tunable nanoparticle size, inexpensive starting materials, maintenance of particle properties, biocompatibility, long-term stability in ethanol, and its translational applicability across different types of synthetic melanins.

[0306]

[0367] Although synthetic melanin materials exhibit attractive properties such as radical scavenging and biocompatibility, their applications outside of aqueous media are limited due to poor solubility. By changing the surface chemistry from hydrophilic to hydrophobic, we have expanded the range of applications not previously possible with the original particles, such as surface assembly and dermal application.

[0307]

[0368] Example 2A: Hydrophobic Melanin via Post-Synthetic Modification for Controlled Self-Assembly

[0369] Allomelanins are a class of nitrogen-free melanins found primarily in fungi and, like all naturally occurring melanins, are hydrophilic. Herein, we develop a facile method for modifying synthetic hydrophilic allomelanins to yield hydrophobic derivatives through post-synthetic modification. A variety of amine-functionalized molecules can be efficiently conjugated to allomelanin nanoparticles under mild conditions with high addition efficiency. Hydrophobicity is imparted by introducing amine-terminated alkyl groups with different chain lengths. We demonstrate that the resulting hydrophobic allomelanin nanoparticles can undergo controlled air / water interfacial self-assembly, enabling the generation of large-scale, uniform structural colors. This work provides an efficient and tunable surface chemistry modification strategy that expands the scope of synthetic melanin structure and function beyond the known diversity found in nature.

[0308]

[0370] Melanins are a group of natural pigments found in most living organisms. 1 In nature, it is structural coloration, 2 radiation protection, 3~5 body temperature regulation, 6~9 and metal chelation 10Synthetic mimetics have been developed to elucidate the structure and function of natural melanin and to further explore various new functions and applications. 11~13 Over the past two decades, polydopamine, used to mimic natural eumelanin, has been the most common synthetic analog. Other synthetic mimics of melanin have received far less attention. 14~19 Allomelanins, the focus of this study, are a nitrogen-free class of melanins often derived from the precursor 1,8-dihydroxynaphthalene (1,8-DHN) and found primarily in fungi. 20~25 Natural allomelanin acts as a protective agent in fungi, allowing them to withstand radiation. 26 Recently, synthetic allomelanin materials have been developed using a chemical synthesis route that polymerizes the monomer 1,8-DHN and related dimers. 27 The resulting allomelanin nanoparticles (AMNPs) possess well-defined nanostructures, diverse morphologies, radical scavenging activity, and high intrinsic microporosity derived from the voids generated within the naphthalene-based polymer network, making them excellent candidate materials for radioprotection and toxin adsorption. 28、29 Indeed, based on these synthetic studies and comparison with naturally occurring materials, the inventors describe it as the first known biopolymer of intrinsic microporosity (BioPIM). 28

[0309]

[0371] Although these synthetic allomelanins possess multiple desirable properties, chemical approaches to tune and modify their surface chemistry have not been described. We reasoned that such an approach would enable access to uniform properties, including dispersion in diverse solvents for processing, controlled assembly, and structural coloration. Here, we describe a facile post-synthetic modification (PSM) that expands the range and versatility of functional groups that can be incorporated into synthetic allomelanins (Figures 1A-1B).

[0310]

[0372] AMNPs were synthesized through the oxidative polymerization of 1,8-DHN ( Figure 1 A). 27The initial resulting material exists as a homogeneous dispersion of nanoparticles, referred to here as fresh AMNPs, composed largely of DHN oligomers (Figure 6). 27 As in our previous work, we observed a visible darkening of the particles in aqueous solution, from gray to black, along with a broadening of the peaks in the UV-Vis absorbance spectra (Figures 7A-B). 28 This process occurs at ambient conditions via a natural oxidation process in air, and in fact this aging process is common for phenolic materials. 30 Aged AMNPs contain incorporated DHN monomers at a higher degree of polymerization, resulting in a more highly cross-linked structure with more quinone moieties. 30 These quinone groups of the aged AMNPs then present potential reactive sites for further chemical modification. Nucleophilic functional groups, such as amines, can then covalently modify the particles via either Michael addition or Schiff base reactions with the quinones (Figure 1A, Figure 6). 31、32 We have demonstrated that these PSMs are a simple yet efficient strategy that can be generally applied to a wide range of amine-functionalized molecules. Specifically, we successfully prepared hydrophobic allomelanins using alkylamines with long carbon chains. The resulting hydrophobic AMNPs can be used to generate large-scale, homogeneous structural colors through self-assembly at the air / water interface.

[0311]

[0373] Synthesis and Characterization of Modified Synthetic Allomelanin Nanoparticles: In this example, AMNPs with different morphologies were prepared as substrates for further surface modification. The morphologies included solid AMNPs (S-AMNPs), walnut AMNPs (W-AMNPs), hollow AMNPs (H-AMNPs), and lace-like AMNPs (L-AMNPs) (Figure 1B). The synthesis was based on previous work (see Example 2B for preparation methods). 27、28To ensure enrichment of quinone groups, after the synthesis of fresh AMNPs, the particles were aged under ambient conditions for 30 days for further oxidation. Transmission electron microscopy (TEM) revealed uniform and well-defined nanostructures for all four types of AMNPs (Figure 1B, Table 1). To test the PSM process, N,N-dimethylethylenediamine (DMEN) was first chosen as the standard amine to functionalize the S-AMNPs (Figures 2A-2D). DMEN contains a relatively large amount of nitrogen for analysis, so it served as a convenient marker of modification. Briefly, S-AMNPs were dispersed in water, followed by the addition of DMEN under vigorous stirring at room temperature. The final concentration of AMNPs was 1.0 mg / mL. After 24 h, the particles were centrifuged and washed with water to obtain S-AMNP-NMe2. S-AMNP-NMe2 remained as well-defined spherical nanoparticles with a diameter (184 ± 3 nm) similar to that of S-AMNP (178 ± 4 nm) (Figure 2A, Table 1). Since the original AMNPs did not contain nitrogen, X-ray photoelectron spectroscopy (XPS) confirmed the modification with nitrogen-containing DMEN (Figure 2B i and Figure 2B ii). In particular, N 1sIn the spectra, C-NH-C and C-NMe2 at 399.7 eV and C=NC at 402.0 eV were observed, indicating successful covalent conjugation between S-AMNP and DMEN (Figure 2B iii and Figure 2B iv). Dynamic light scattering (DLS) showed some aggregation after modification, with the hydrodynamic diameter increasing from 220.3 nm to 475.7 nm at neutral pH and subsequent pH dependence consistent with an amine-functionalized surface (Figure 2C i). We believe this is consistent with the introduction of colloidal instability as the surface chemistry is modified. To further explore this phenomenon, zeta potential measurements were performed upon modification and compared with the pristine AMNP (Figure 2C ii). Specifically, AMNPs possess a sufficiently negative zeta potential (-28.8 mV) to maintain a stable suspension. In turn, the dimethylamino group of DMEN incorporated to yield S-AMNP-NMe2 results in a positive surface charge (23.7 mV). The decrease in size at neutral pH, manifested as a more aggregated solution, confirms the incorporation of functional groups. Furthermore, both DLS and zeta potential measurements showed a pH dependence for both S-AMNP and S-AMNP-NMe2. As the pH increased, the zeta potential decreased to -55 mV for both particles at pH 11 (Figure 2C ii). Conversely, for S-AMNP-NMe2 at low pH, the zeta potential reached +35 mV, restoring colloidal stability to the now protonated particles bearing the cationic tertiary amine. Elemental analysis was then applied to quantitatively determine the addition efficiency (carbon, hydrogen, nitrogen, sulfur). These data revealed that the nitrogen percentage increased from zero (S-AMNP) to 5.31% (S-AMNP-NMe2) after modification (Table 2). The molar ratio of DMEN to DHN structural units was calculated to be 0.40 (FIG. 8).

[0312] [Table 1]

[0313] [Table 2]

[0314]

[0374] Scanning TEM (STEM) energy dispersive X-ray (EDX) spectroscopy (STEM-EDX) was performed to generate an elemental map of S-AMNP-NMe2, which revealed uniformly distributed nitrogen signals similar to C and O (Figure 2D). This indicates that these synthetic allomelanins are 600–800 m 2 This is consistent with the fact that the samples were found to exhibit intrinsic microporosity with BET areas in the range of 1 / g. 28 Therefore, DMEN can diffuse into the micropores and functionalize the interior. To look for any changes in porosity caused by the modification, N2 gas physisorption measurements were carried out at 77 K. The nitrogen isotherm was 565 m for S-AMNPs. 2 / g, 70m for S-AMNP-NMe2 2 The Brunauer-Emmett-Teller (BET) area of ​​1000 nm / g was revealed (Figures 9A-9B). DFT calculations indicated a primary pore of approximately 6.8 Å for S-AMNP, while no corresponding pores were observed for S-AMNP-NMe2, along with a significant decrease in pore volume, consistent with the micropores being occupied by DMEN. To further confirm the presence of nitrogen within the particles, S-AMNP-NMe2 was ultra-thinly sectioned into 50 nm sections and imaged via STEM-EDX, revealing a similar uniform distribution of nitrogen (Figure 10). Combining the distribution of nitrogen in the STEM-EDX mapping with the decrease in porosity, the evidence suggests that modification occurred both on the surface and, to some extent, within the interior of the AMNPs. Finally, this PSM strategy was applied to AMNPs with different morphologies (Figure 1B). XPS characterization again confirmed the presence of DMEN covalently bound to W-AMNP, H-AMNP, and L-AMNP (Figures 11A-C). In addition, the zeta potentials of all types of AMNP revealed a switch from negative to positive values ​​(Figures 12A-D).

[0315]

[0375] Synthesis and characterization of hydrophobic allomelanin nanoparticles: Like other melanin-based materials, AMNPs have excellent colloidal dispersibility in aqueous solutions due to the hydrophilic hydroxyl groups on their surface, while their dispersibility in nonpolar organic solvents is very poor. Therefore, after proving the feasibility of the PSM strategy, we used hexylamine (C6-NH2) and octadecylamine (C6-NH2) as colloidal dispersants. 18 -NH2) with the goal of generating hydrophobic analogs (Figures 3A-E).

[0316]

[0376] Briefly, AMNPs were mixed with amine-functionalized alkanes in ethanol (EtOH) for 24 h, followed by centrifugation and washing with EtOH. The resulting particles were named S-AMNP-C6 and S-AMNP-C, respectively. 18 (Figure 3A). S-AMNP-C6 and S-AMNP-C 18 XPS characterization of S-AMNP showed a significant nitrogen signal, confirming successful conjugation (Figure 3B). DLS showed a peak at 278 nm for S-AMNP, 222 nm for S-AMNP-C6, and 242 nm for S-AMNP-C6 in ethanol. 18 The hydrodynamic diameter of the modified hydroxyl group was 225 nm (Fig. 3Ci). The UV-vis absorbance spectra showed similar characteristics before and after modification (Fig. 13). The peak at 2955 cm corresponds to the symmetric and asymmetric stretching vibrations of the aliphatic hydrocarbon groups from C6-NH2. -1 , 2929cm -1 , 2868cm -1 , and 2858 cm -1 A new characteristic peak at 2925 cm was observed in the Fourier transform infrared (FTIR) spectrum of S-AMNP-C6 (Figure 3C ii). -1 and 2852 cm -1 A similar peak was observed in S-AMNP-C. 18 The nitrogen isotherm of S-AMNP was observed at 565 m 2 / g, 85m of S-AMNP-C6 2 / g and S-AMNP-C 18 45m 2The decrease in BET surface area to 1000 kJ / g was revealed (Figures 14A-14B). 18 STEM-EDX mapping of the revealed a uniform distribution of nitrogen on the spherical particles (Figure 15).

[0317]

[0377] To further investigate the results of chemical modification, S-AMNP, S-AMNP-C6, and S-AMNP-C were analyzed in water and different organic solvents (dichloromethane (CH2Cl2), chloroform (CHCl3), toluene, ethyl acetate, hexane, and cyclohexane). 18 Dispersions of S-AMNP-C6 were investigated (Figure 16). Qualitatively, S-AMNP-C6 was found in the aqueous phase in all cases. 18 The S-AMNP-C dispersed in the organic phase (CHCl, CHCl, and ethyl acetate) or remained in the aqueous phase (toluene, hexane, and cyclohexane) (Figure 3D, Figure 17). To quantitatively measure hydrophobicity, AMNPs were dispersed in THF (10 mg / mL) and then drop-cast onto glass slides to fabricate films for water contact angle measurements. As expected, S-AMNP-C 18 The coating with S-AMNP-C6 had the highest water contact angle (130.0 ± 0.8°) (Figure 3E). S-AMNP-C6 also exhibited high hydrophobicity (119.4 ± 0.2°) compared to S-AMNP (41.9 ± 0.2°) (Figure 3E). Furthermore, we note that PSM can be generalized to other primary amines. Modification with 5-amino-1-pentanol, t-butylamine, 10-amino-1-decanol, 1,6-hexanediamine, and 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononylamine was confirmed using XPS (Figures 18A–18E). In addition to small molecules, polymers with amine-functionalized end groups were also investigated in PSM. Polyethylene glycol amines (mPEG-NH) with different molecular weights (MW 550, MW 2000) were utilized to functionalize AMNPs. The results were analyzed by detecting the nitrogen signal using XPS (Figures 29A-29B) and by detecting the characteristic peak corresponding to PEG using FTIR (2872 cm for C-H stretching). -1, CO stretching is 1416 cm -1 , 1348cm -1 , 1252 cm for CH bending angle -1 , 1085cm -1 ) (Figure 30) confirmed the modification.

[0318]

[0378] Air / water interfacial self-assembly of hydrophobic allomelanin nanoparticles: As natural pigments with high refractive index and broadband absorption, natural and synthetic melanins with diverse morphologies have become attractive materials for the generation of structural colors. 33 Dip coating, 34 spray coating, 35 Inkjet printing, 36 Although numerous strategies, including inverse emulsion self-assembly and reverse emulsion self-assembly, have been applied to generate structural colors using melanin materials, 37、38 Achieving large-area ordered structural colors remains a challenge. Air / water interfacial self-assembly has been elucidated as a versatile approach for the fast and controlled self-assembly of various micro- and nanoscale materials, such as silica nanoparticles, gold nanoparticles, and polymeric micro / nanospheres, to form layered and two-dimensional arrays. 39~42 We reasoned that hydrophobic allomelanin nanoparticles would be amenable to this approach, achieving large-area, homogeneous thin films with close-packed arrangements and controlled multilayers; therefore, we investigated the process and morphology dependence on color and packing (Figures 4A-G).

[0319]

[0379] Allomelanin nanoparticles with different structures (S-AMNP, W-AMNP, H-AMNP, and L-AMNP) were synthesized and C 18 The AMNP-C was further modified with -NH2. The modification was confirmed using XPS (Figures 19A-19B). Before adding the colloidal suspension, a transfer substrate (silicon wafer) was placed at the bottom of a container filled with Milli-Q water. 18was ultrasonically dispersed in 1-butanol at a concentration of 2.0 mg / mL. This colloidal suspension was slowly added to the water surface using a pipette. 18 The continuous addition of 18 This led to the formation of a monolayer. Once the water surface was fully occupied, the monolayer could be transferred to the substrate by either draining the water or lifting the substrate. W-AMNP-C on a silicon wafer (1 cm × 1 cm) 18 A typical photograph of the monolayer of AMNP-C showed a homogeneous blue color to the naked eye (Figure 4A). A top-view scanning electron microscope (SEM) image of the monolayer film showed the uniform blue color of pseudohexagonal close-packed AMNP-C, which was confirmed by the corresponding two-dimensional fast Fourier transform (FFT). 18 The irregular walnut-shaped AMNP-C 18 All of the nanoparticles, including those shown in Figure 20A, had a pseudo-hexagonal close-packed structure (SEM image, Figure 20A and atomic force microscope image, Figure 21).

[0320]

[0380] The fact that the particles were reliably localized at the interface enabled the fabrication of multilayered coatings via layer-by-layer self-assembly. By repeating the transfer procedure multiple times, multilayered coatings with the desired number of layers could be achieved (Figure 4A). Monolayer (L1), bilayer (L2), trilayer (L3), and quadruple layer (L4) coatings of hydrophobic allomelanin nanoparticles with different morphologies (solid, walnut, hollow, and lace-like) were successfully obtained. Cross-sectional SEM images of all four types of AMNP-C 18 The characteristics of L1, L2, L3, and L4 were confirmed for each film (Figures 4D-4G), which show a homogeneous assembly of one to four layers over a large area. The thickness of each film was summarized (Figure 31). The uniform structural color produced by the thin films was captured using optical microscopy (Figures 4D-4G) and the corresponding reflectance spectra (Figures 4C, 22A-22C) and visualized on the CIE 1931 chromaticity diagram, which is based on human color vision (Figure 32). These results demonstrated a fast and accurate method for fabricating large two-dimensional arrays of melanin nanoparticles with well-defined layers.

[0321]

[0381] Conclusion of Example 2A: We have developed an effective strategy for functionalizing synthetic allomelanin nanoparticles. Surface properties can be tuned using amines bearing desired functional groups. Specifically, targeted hydrophobic allomelanins were successfully prepared by covalently incorporating long carbon chains. This hydrophobic feature was exemplified through the controlled air / water interfacial self-assembly of allomelanin nanoparticles with different shapes, which produced large areas of uniform structural color with precise alignment and defined particle layers. We envision that this PSM method will be useful for obtaining melanin-based materials with more diverse functionalities than are possible with either the natural product itself or its non-functionalized synthetic analogs.

[0322]

[0382] Exemplary Experimental Embodiments of Example 2A:

[0383] Synthesis of solid AMNPs (S-AMNPs): S-AMNPs were synthesized in almost the same manner as AMNP-1 in the previous study. 27 Briefly, 1,8-DHN (150 mg) was dissolved in 7.5 mL of acetonitrile in a round-bottom flask. To this solution, 142.5 mL of Milli-Q water was added, and the mixture was stirred for 5 minutes, after which 1 mL of a 1 N NaIO solution in water was rapidly injected. The reaction turned yellow and then quickly turned gray after the oxidant was injected. The reaction was stirred for 20 hours, then purified by centrifugation at 11,500 rpm for 10 minutes, followed by three cycles of washing by redispersion in Milli-Q water. After the final wash, the particles were resuspended in 12 mL of Milli-Q water in a 50 mL Falcon tube and stored capped at room temperature under ambient conditions.

[0323]

[0384] General procedure for natural oxidation (aging) of AMNPs: After obtaining fresh S-AMNPs and W-AMNPs, particles suspended in Milli-Q water in 50 mL Falcon tubes were stored at room temperature, capped, and kept under ambient conditions for 30 days for further natural oxidation and crosslinking. H-AMNPs and L-AMNPs were synthesized from purified batches of fresh S-AMNPs. After a certain amount of processing time to obtain purified H-AMNPs (9 days) and L-AMNPs (10 days), these particles suspended in Milli-Q water in 50 mL Falcon tubes were stored at room temperature, capped, and kept under ambient conditions for an additional 21 and 20 days, respectively, for further natural oxidation and crosslinking.

[0324]

[0385] General procedure for post-synthetic modification: Briefly, AMNP (5 mg) was dispersed in water in a glass vial. To this solution, an amine (3.0 equivalents relative to the DHN unit) dissolved in water was added. The final concentration of AMNP was 1.0 mg / mL. The mixture was stirred for 24 hours, then purified by centrifugation at 11,500 rpm for 10 minutes, followed by three cycles of washing by redispersion in Milli-Q water. For amines with poor solubility in water, EtOH was selected as a dispersant for AMNP and amine to replace water.

[0325]

[0386] General procedure for air / water interfacial self-assembly: Briefly, AMNP-C 18 was dispersed in 1-butanol at a concentration of 2.0 mg / mL and then sonicated for 15 minutes. A clean container (e.g., a hexagonal plastic cup, a Petri dish, a well plate, or a beaker) filled with Mili-Q water was used throughout the self-assembly process. AMNP-C in 1-butanol 18 was slowly add...

Claims

1. A surface functionalized with a modifier via a linker group A functionalized artificial melanin material comprising: the modifying agent comprises the linker group and a functional group attached to the linker group; The functionalized artificial melanin material, wherein the linker group is a nucleophilic group.

2. 2. The functionalized artificial melanin material of claim 1, comprising functionalized artificial melanin nanoparticles, each functionalized artificial melanin nanoparticle independently comprising a surface functionalized with said modifying agent via said linker group.

3. 3. The functionalized artificial melanin material of claim 1, wherein the linker group is an amine group, a thiol group, or any combination thereof.

4. The functionalized artificial melanin material of claim 3 , wherein the linker group is an amine group.

5. The functionalized artificial melanin material of claim 4 , wherein the linker group is a primary amine group.

6. The linker group may be of formula FX1A or FX1B: 【Chemistry 1】 The functionalized artificial melanin material according to any one of claims 1 to 5, characterized by:

7. The functionalized artificial melanin material according to any one of claims 1 to 6, wherein the functional group is hydrophobic or confers hydrophobicity to the functionalized artificial melanin material or its functionalized artificial melanin nanoparticles.

8. 8. The functionalized artificial melanin material according to any one of claims 1 to 7, which is hydrophobic and / or forms a stable colloid in a non-aqueous hydrophobic solvent at a concentration of said material selected from the range of 0.5 mg / mL to 100 mg / mL.

9. The functionalized artificial melanin material according to any one of claims 1 to 8, wherein a dispersion or formulation having the functionalized artificial melanin material or its functionalized artificial melanin nanoparticles at a concentration selected from the range of 0.5 mg / mL to 100 mg / mL is characterized by a contact angle of at least 90°.

10. The functionalized artificial melanin material according to any one of claims 1 to 9, wherein a dispersion or formulation having the functionalized artificial melanin material or its functionalized artificial melanin nanoparticles at a concentration selected from the range of 0.5 mg / mL to 100 mg / mL is characterized by a contact angle selected from the range of 125° to 160°.

11. The functionalized artificial melanin material according to any one of claims 1 to 10, wherein the functionalized artificial melanin material or the functionalized artificial melanin nanoparticles thereof have a zeta potential of -20 mV or more when dispersed in water or a non-aqueous hydrophobic solvent at a concentration selected from the range of 0.5 mg / mL to 100 mg / mL.

12. The modifying agent has the formula FX2A or FX2B: 【Chemistry 2】 (wherein X is the functional group) The functionalized artificial melanin material according to any one of claims 1 to 11, characterized by:

13. 13. The functionalized artificial melanin material according to any one of claims 1 to 12, wherein each linker group is independently attached to a phenyl group or a quinone of the artificial melanin material or of each artificial melanin nanoparticle.

14. 14. The functionalized artificial melanin material according to any one of claims 1 to 13, wherein the modifying agent bound to the artificial melanin material or to the respective functionalized artificial melanin nanoparticles is a product of Michael addition or via Schiff base reaction.

15. The functionalized artificial melanin material according to any one of claims 1 to 14, wherein the linker group of the modifying agent is attached to the outer surface of the functionalized artificial melanin material or to the outer surface of the functionalized artificial melanin nanoparticles, or to the inner pore surface of the functionalized artificial melanin material or to the inner pore surface of the functionalized artificial melanin nanoparticles, or both.

16. 16. The functionalized artificial melanin material according to any one of claims 1 to 15, wherein at least a portion of the functionalized artificial melanin material or its functionalized artificial melanin nanoparticles comprises at least two different modifiers.

17. The functionalized artificial melanin material according to any one of claims 1 to 16, comprising at least 5% by weight of said modifying agent.

18. A functionalized artificial melanin material according to any one of claims 1 to 17, wherein the functional group faces a solution or environment to which the functionalized artificial melanin material or its functionalized artificial melanin nanoparticles are exposed.

19. The functional group is a substituted or unsubstituted C ４ ~C ３０ Hydrocarbyl group, substituted or unsubstituted C ４ ~C ３０ alkyl group, substituted or unsubstituted C ４ ~C ３０ Cycloalkyl groups, substituted or unsubstituted C ４ ~C ３０ an aryl group, substituted or unsubstituted C ４ ~C ３０ Heteroaryl group, substituted or unsubstituted C ４ ~C ３０ Acyl group, substituted or unsubstituted C ４ ~C ３０ Alkoxy group, substituted or unsubstituted C ４ ~C ３０ Alkenyl group, substituted or unsubstituted C ４ ~C ３０ Alkynyl group, substituted or unsubstituted C ４ ~C ３０ 19. The functionalized artificial melanin material according to any one of claims 1 to 18, wherein the functionalized artificial melanin material is selected from the group consisting of alkyl, aryl, and any combination thereof.

20. The functional group is C ４ ~C ３０ Alkyl group, C ４ ~C ３０ Alkenyl group, C ４ ~C ３０ 20. The functionalized artificial melanin material according to any one of claims 1 to 19, wherein the aryl group is selected from the group consisting of alkynyl groups, aryl groups, and any combination thereof.

21. The functional group is a substituted or unsubstituted C ６ ~C ３０ The functionalized artificial melanin material according to any one of claims 1 to 20, wherein the functionalized artificial melanin material is a hydrocarbyl group.

22. The functional group is a substituted or unsubstituted C ６ ~C ３０ The functionalized artificial melanin material according to any one of claims 1 to 21, which is an alkyl group.

23. The functional group is a substituted or unsubstituted C ８ ~C ２４ The functionalized artificial melanin material according to any one of claims 1 to 22, wherein the functionalized artificial melanin material is an alkyl group.

24. The functional group is a substituted or unsubstituted C ４ ~C ３０ Hydrocarbyl group, substituted or unsubstituted C ４ ~C ３０ alkyl group, substituted or unsubstituted C ４ ~C ３０ Cycloalkyl groups, substituted or unsubstituted C ４ ~C ３０ an aryl group, substituted or unsubstituted C ４ ~C ３０ Heteroaryl group, substituted or unsubstituted C ４ ~C ３０ Acyl group, substituted or unsubstituted C ４ ~C ３０ Alkoxy group, substituted or unsubstituted C ４ ~C ３０ Alkenyl group, substituted or unsubstituted C ４ ~C ３０ Alkynyl group, substituted or unsubstituted C ４ ~C ３０ The functionalized artificial melanin material according to any one of claims 1 to 18, wherein the functionalized artificial melanin material is selected from the group consisting of alkylaryl groups, substituted or unsubstituted hydroxyl groups, substituted or unsubstituted carbonyl groups, substituted or unsubstituted sulfide groups, substituted or unsubstituted thiol groups, substituted or unsubstituted phosphate groups, substituted or unsubstituted azo groups, substituted or unsubstituted cyanate groups, substituted or unsubstituted primary amine groups, substituted or unsubstituted secondary amine groups, substituted or unsubstituted tertiary groups, substituted or unsubstituted imine groups, substituted or unsubstituted nitrile groups, substituted or unsubstituted pyridinyl groups, substituted or unsubstituted diamine groups, substituted or unsubstituted triamine groups, substituted or unsubstituted azide groups, substituted or unsubstituted diimine groups, substituted or unsubstituted triimine groups, substituted or unsubstituted amide groups, substituted or unsubstituted diimide groups, substituted or unsubstituted ether groups, and any combination thereof.

25. The functional group is a substituted or unsubstituted C ４ ~C ３０ Hydrocarbyl group, substituted or unsubstituted C ４ ~C ３０ alkyl group, substituted or unsubstituted C ４ ~C ３０ Cycloalkyl groups, substituted or unsubstituted C ４ ~C ３０ an aryl group, substituted or unsubstituted C ４ ~C ３０ Heteroaryl group, substituted or unsubstituted C ４ ~C ３０ Acyl group, substituted or unsubstituted C ４ ~C ３０ Alkoxy group, substituted or unsubstituted C ４ ~C ３０ Alkenyl group, substituted or unsubstituted C ４ ~C ３０ Alkynyl group, substituted or unsubstituted C ４ ~C ３０ The functionalized artificial melanin material according to any one of claims 1 to 18 and 24, wherein the functionalized artificial melanin material is selected from the group consisting of alkylaryl groups, substituted or unsubstituted primary amine groups, substituted or unsubstituted secondary amine groups, substituted or unsubstituted tertiary amine groups, and any combination thereof.

26. The functionalized artificial melanin material according to any one of claims 1 to 18, 24 and 25, wherein each modifier is independently selected from the group consisting of 1-hexylamine, 3,3-dimethylbutylamine, octadecylamine, 5-amino-1-pentanol, t-butylamine, 10-amino-1-decanol, 1,6-hexanediamine, and 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononylamine.

27. 27. The method of any one of claims 1 to 26, wherein the functionalized artificial melanin material comprises an amorphous functionalized artificial melanin material.

28. 28. The functionalized artificial melanin material according to any one of claims 1 to 27, wherein each of said functionalized artificial melanin material or its functionalized artificial melanin nanoparticles is not bound to, conjugated to, attached to, coated by, encapsulated by, or otherwise chemically associated with a natural or biological proteinaceous matrix, component, or lipid.

29. 29. The functionalized artificial melanin material of any one of claims 1 to 28, wherein each of the functionalized artificial melanin material or its functionalized artificial melanin nanoparticles is characterized as a eumelanin, a pheomelanin, an allomelanin, or a combination thereof.

30. 30. The functionalized artificial melanin material of any one of claims 1 to 29, comprising artificial allomelanin nanoparticles, artificial polydopamine nanoparticles, or any combination thereof.

31. The functionalized artificial melanin material or the functionalized artificial melanin nanoparticles thereof is porous, and the porous size is 70 mm. ２ / g~800m ２ 31. The functionalized artificial melanin material according to any one of claims 1 to 30, having a Brunauer-Emmett-Teller (BET) area selected from the range of 1 / g.

32. The functionalized artificial melanin material or the functionalized artificial melanin nanoparticles thereof is non-porous or has a thickness of 20 mm or less. ２ 32. The functionalized artificial melanin material of any one of claims 1 to 31, having a Brunauer-Emmett-Teller (BET) area of ​​less than 1 / g.

33. 33. The method of any one of claims 1 to 32, wherein the functionalized artificial melanin material comprises functionalized artificial melanin particles having an average cross-sectional size selected from the range of 10 nm to 1000 nm, as measured by transmission electron microscopy and / or dynamic light scattering.

34. 34. The method of any one of claims 1 to 33, wherein the functionalized artificial melanin material comprises functionalized artificial melanin particles having an average cross-sectional size selected from the ranges of 10 nm to 100 nm, 100 nm to 500 nm, or a combination thereof, as measured by transmission electron microscopy and / or dynamic light scattering.

35. 35. The functionalized artificial melanin material according to any one of claims 1 to 34, characterized by a DPPH radical scavenging activity of at least 30% for 50 μg of said functionalized artificial melanin material.

36. The functionalized artificial melanin material according to any one of claims 1 to 35, which is a thin film.

37. 37. The functionalized artificial melanin material of claim 36, wherein the thin film exhibits structural color.

38. 38. The functionalized artificial melanin material of claim 36 or 37, wherein the thin film comprises one or more monolayers of the functionalized artificial melanin nanoparticles.

39. 39. The functionalized artificial melanin material of any one of claims 36 to 38, wherein the thin film comprises one, two, three, or four monolayers of the functionalized artificial melanin nanoparticles.

40. 40. The functionalized artificial melanin material of any one of claims 36 to 39, wherein the thin film is at a liquid-liquid interface, at a liquid-gas interface, or on a substrate.

41. The thin film is 0.25 cm ２ ~9cm ２ The functionalized artificial melanin material according to any one of claims 36 to 40, having an area selected from the range of:

42. The functionalized artificial melanin material according to any one of claims 36 to 41, wherein the thin film is on the skin.

43. one or more hydrophobic solvents; The functionalized artificial melanin material according to any one of claims 1 to 42, dispersed in one or more solvents. A melanin-containing preparation comprising:

44. one or more hydrophobic solvents; a functionalized artificial melanin material dispersed in the one or more solvents; A melanin-containing preparation comprising: The functionalized artificial melanin material comprises a surface functionalized with a modifying agent via a linker group; the modifying agent comprises the linker group and a functional group attached to the linker group; A melanin-containing preparation, wherein the linker group is a nucleophilic group.

45. 45. The melanin-containing formulation of claim 43 or 44, wherein the functionalized artificial melanin material comprises functionalized artificial melanin nanoparticles, each of which independently comprises a surface functionalized with the modifying agent via the linker group.

46. The melanin-containing preparation according to any one of claims 43 to 45, wherein the concentration of the artificial melanin material in the melanin preparation is selected from the range of 0.5 mg / mL to 100 mg / mL.

47. The melanin-containing preparation according to any one of claims 43 to 46, wherein the concentration of the functionalized artificial melanin nanoparticles is selected from the range of 0.5 mg / mL to 100 mg / mL.

48. 48. The melanin-containing formulation according to any one of claims 43 to 47, characterized by a contact angle of at least 90°.

49. 49. The melanin-containing preparation according to any one of claims 43 to 48, characterized by a contact angle selected from the range of 125° to 160°.

50. 50. The melanin-containing formulation according to any one of claims 43 to 49, wherein the dispersed functionalized artificial melanin nanoparticles are characterized by a zeta potential magnitude of greater than 20.

51. The melanin-containing formulation according to any one of claims 43 to 50, wherein the dispersed functionalized artificial melanin nanoparticles are characterized by a zeta potential of -40 mV or greater.

52. 52. The melanin-containing formulation according to any one of claims 43 to 51, wherein the dispersed functionalized artificial melanin nanoparticles are characterized by a positive zeta potential.

53. 53. The melanin-containing formulation of any one of claims 43 to 52, characterized as a stable colloid.

54. 54. The melanin-containing formulation of any one of claims 43 to 53, which is an ointment, cream, gel, paste, or any combination thereof.

55. 55. The melanin-containing formulation according to any one of claims 43 to 54, wherein the one or more hydrophobic solvents are organic solvents.

56. 56. The melanin-containing formulation of any one of claims 43 to 55, wherein the one or more hydrophobic solvents constitute at least 60% of the total solvent concentration in the formulation.

57. 57. The melanin-containing formulation of any one of claims 43 to 56, wherein the one or more hydrophobic solvents are at least 60 vol. % of the formulation.

58. The melanin-containing preparation according to any one of claims 43 to 57, having 40 vol. % or less of water.

59. 59. The melanin-containing formulation of any one of claims 43-58, wherein the one or more hydrophobic solvents comprise dichloromethane, chloroform, tetrahydrofuran, toluene, ethyl acetate, hexane, cyclohexane, squalene, squalene, petrolatum, a petrolatum-containing solvent or solvent mixture, petrolatum ointment, a petrolatum-based ointment, or any combination thereof.

60. 60. The melanin-containing formulation of any one of claims 43 to 59, wherein the one or more hydrophobic solvents comprise petrolatum or petrolatum.

61. The melanin-containing formulation according to any one of claims 43 to 60, comprising an organogel.

62. 62. The melanin-containing formulation of any one of claims 43 to 61, wherein the one or more hydrophobic solvents are solvent formulations suitable as carriers for wound healing.

63. 63. The melanin-containing formulation of any one of claims 43 to 62, which is a sunscreen or sunblock product for application to the skin; wherein the functionalized artificial melanin material is provided in the formulation to promote skin healing in the event of UV-induced skin damage.

64. 64. The melanin-containing preparation according to any one of claims 43 to 63, having a viscosity selected from the range of 12 cP to 64,000 cP at 25°C measured using a viscometer and / or rheometer.

65. 65. The melanin-containing formulation of any one of claims 43 to 64, which is therapeutically effective in promoting skin healing when administered to damaged skin.

66. 1. A method for treating a subject, comprising: topically administering to the damaged skin of the subject a melanin preparation according to any one of claims 43 to 65; The melanin preparation comprises a functionalized artificial melanin material according to any one of claims 1 to 35; administering the functionalized artificial melanin material to the damaged skin comprises an extracellular functionalized artificial melanin material; promoting healing of the damaged skin through at least the extracellular functionalized artificial melanin material; said step of promoting skin healing includes at least a portion of said extracellular artificial melanin material exerting a therapeutic extracellular activity; A method comprising:

67. 1. A method for treating a subject, comprising: topically administering a melanin preparation to the damaged skin of the subject; The functionalized artificial melanin material comprises a surface functionalized with a modifier via a linker group; the modifying agent comprises the linker group and a functional group attached to the linker group; the linker group is a nucleophilic group; The melanin formulation comprises one or more hydrophobic solvents and the functionalized artificial melanin material dispersed in the one or more hydrophobic solvents; administering the functionalized artificial melanin material to the damaged skin comprises an extracellular functionalized artificial melanin material; promoting healing of the damaged skin through at least the extracellular functionalized artificial melanin material; said step of promoting skin healing includes at least a portion of said extracellular artificial melanin material exerting a therapeutic extracellular activity; A method comprising:

68. 68. The method of claim 66 or 67, wherein the functionalized artificial melanin material comprises functionalized artificial melanin nanoparticles, each of which independently comprises a surface functionalized with the modifying agent via the linker group.

69. 69. The method of any one of claims 66 to 68, wherein the damaged skin is a closed wound or an open wound.

70. 70. The method of any one of claims 66 to 69, wherein the damaged skin is associated with thermally induced damage, chemically induced damage, radiation induced damage, mechanical friction damage, and / or infected cellulitis induced damage.

71. 71. The method of claim 70, wherein the radiation-induced damage is UV-induced damage and the chemically-induced damage is mustard-induced damage.

72. 72. The method of any one of claims 66 to 71, wherein the damaged skin comprises one or more of blisters, vesicles, and denuded skin.

73. 73. The method of any one of claims 66 to 72, wherein at least a portion of the extracellular melanin material is within the stratum corneum of the damaged skin.

74. 74. The method of any one of claims 66-73, wherein the damaged skin comprises extracellular free radical species; and the therapeutic extracellular activity comprises the at least a portion of the extracellular artificial melanin material quenching at least the extracellular free radical species.

75. 75. The method of claim 74, wherein the extracellular free radical species comprises reactive oxygen species.

76. 76. The method of claim 74 or 75, wherein at least a portion of the quenched extracellular free radical species is within the stratum corneum.

77. 77. The method of any one of claims 66 to 76, wherein the damaged skin comprises inflammation; and the step of promoting skin healing comprises at least a portion of the administered artificial melanin material directly and / or indirectly reducing the inflammation.

78. 78. The method of any one of claims 66 to 77, wherein the therapeutic extracellular activity comprises that said at least a portion of said extracellular artificial melanin material directly and / or indirectly reduces inflammation.

79. 79. The method of any one of claims 66 to 78, wherein directly and / or indirectly reducing the inflammation comprises at least a portion of the administered artificial melanin adsorbing one or more inflammatory factors, one or more factors, one or more scarring and / or fibrosis factors, or any combination thereof.

80. 80. The method of any one of claims 66 to 79, wherein directly and / or indirectly reducing the inflammation comprises at least a portion of the extracellular artificial melanin adsorbing one or more extracellular inflammatory factors, one or more extracellular enzymatic factors, one or more extracellular scarring and / or fibrosis factors, or any combination thereof.

81. 81. The method of claim 80, wherein the one or more inflammatory factors and / or one or more enzymatic factors comprise TNFα, iNOS, MMP9, MMP3, MMP9, CXCL1, one or more proteins associated with the MAPK / ERK pathway, and / or one or more enzymes associated with the MAPK / ERK pathway.

82. 82. The method of any one of claims 79 to 81, wherein at least a portion of the adsorbed inflammatory factor and / or the adsorbed extracellular enzymatic factor is within the stratum corneum.

83. 83. The method of any one of claims 66 to 82, wherein the promoting step comprises at least a portion of the administered artificial melanin directly and / or indirectly downregulating inflammation-related genes and / or apoptosis-related genes and / or collagen-degrading enzymes and / or fibroblast scarring and fibrosis genes compared to when the artificial melanin material is not present.

84. 84. The method of any one of claims 66 to 83, wherein the promoting step comprises at least a portion of the administered artificial melanin directly and / or indirectly inhibiting apoptosis compared to when the artificial melanin material is not present.

85. 85. The method of any one of claims 66 to 84, wherein at least 50% of the administered artificial melanin material is the extracellular artificial melanin material.

86. 86. The method of any one of claims 66 to 85, wherein the extracellular artificial melanin material is extracellular as long as it is present in the damaged skin.

87. 87. The method of any one of claims 66-86, wherein the step of promoting skin healing further comprises at least a portion of the administered artificial melanin material exerting a therapeutic intracellular activity.

88. the therapeutic intracellular activity is quenching intracellular free radical species; and / or A step of adsorbing one or more intracellular inflammatory factors and / or one or more intracellular enzymatic factors.

88. The method of claim 87, comprising:

89. The skin healing Reduction of the wound area containing damaged tissue; reducing the inflammation of the damaged skin; an increase in superoxide dismutase activity in the damaged skin; a reduction in the bifold skin thickness of the damaged skin; a reduction in edema of the damaged skin; a reduction in the time to scabbing of the damaged skin; a reduction in the depth of injury to said damaged skin; stabilizing the epithelial layer of the damaged skin; a reduction in scar collagen formation in said damaged skin; or any combination thereof 89. The method of any one of claims 66 to 88, comprising:

90. the skin healing has less of the following healing properties than the same one or more healing properties in the absence of the artificial melanin material during the skin healing: a) the total time to reduce the amount or concentration of damaged tissue to 30% of that immediately prior to administering the melanin preparation; b) the total time to reduce inflammation of the damaged skin by 40% of that immediately prior to administering the melanin preparation; c) the total time required for the lesion to reduce to 25% of its double-fold skin thickness immediately prior to administration of the melanin preparation; d) the total time required to reduce the edema of the damaged skin by 25% of that immediately before administering the melanin preparation; e) the total time required to reduce the depth of injury of the damaged skin to 30% of that immediately prior to administering the melanin preparation; f) total time to eschar within the area; or g) any combination thereof 90. The method according to any one of claims 66 to 89, characterized by one or more of the following:

91. said skin healing exhibits the following healing properties to a greater extent than the same one or more healing properties in the absence of said artificial melanin material during said skin healing: a) the rate of reduction of the wound area containing said damaged skin; b) the rate at which inflammation of said damaged skin is reduced; c) the rate of decrease in the double-fold skin thickness of the damaged skin; d) the rate at which the edema of the damaged skin is reduced; e) the rate of reduction in the depth of injury of said damaged skin; f) the rate of stabilization of the epidermal layer of the damaged skin; g) the activity of superoxide dismutase in said damaged skin; h) reducing scar collagen formation in the damaged skin; or i) any combination thereof 91. The method according to any one of claims 66 to 90, characterized by one or more of the following:

92. 92. The method of any one of claims 66 to 91, wherein the skin healing comprises a 20% to 50% reduction in one or more inflammatory factors and / or one or more enzymatic factors in the damaged skin over 72 hours.

93. The skin healing (i) a 30-50% reduction in CXCL1 in the injured skin over 72 hours; (ii) a 20-30% reduction in MMP3 in the injured skin over 72 hours; (iii) a 40% reduction in MMP9 in the injured skin at 72 hours; (iv) a 30-40% reduction in Col3a1 in the injured skin over 72 hours; (v) a reduction in one or more proteins associated with the MAPK / ERK pathway in the damaged skin at 72 hours; (vi) an increase in one or more markers, including CD31, associated with angiogenesis (vascularization) of the damaged skin at 72 hours; (vii) a 20-30% decrease in osm, IL-8, ccl20, and / or ICAM1 in the injured skin over 72 hours; (viii) or any combination thereof 93. The method of any one of claims 66 to 92, comprising:

94. 94. The method of any one of claims 66 to 93, wherein the melanin preparation comprises one or more additives.

95. 95. The method of any one of claims 66 to 94, wherein the melanin formulation does not include artificial melanin materials that have been loaded with or functionalized with non-melanin therapeutic agents.

96. 96. The method of any one of claims 66 to 95, wherein the melanin formulation does not comprise hollow and / or semi-hollow melanin particles carrying non-melanin therapeutic agents.

97. 97. The method of any one of claims 66 to 96, wherein the melanin formulation does not include a non-melanin therapeutic agent.

98. 98. The method of any one of claims 66-97, wherein the melanin formulation is such that the administering step comprises forming a layer of the artificial melanin material on at least a portion of the damaged skin.

99. 99. The method of any one of claims 66-98, wherein the administering step occurs after a skin trauma event has occurred in the area of ​​the subject.

100. 100. The method of any one of claims 66 to 99, comprising the step of wounding the skin prior to the administering step to form the wounded skin.

101. 101. The method of any one of claims 66 to 100, comprising repeating the administering step.

102. 102. The method of any one of claims 66 to 101, wherein the subject is a mammal and / or the skin to be healed is mammalian skin.

103. 103. The method of any one of claims 66 to 102, wherein the melanin formulation is characterized as an ointment, a cream, a gel, a paste, or any combination thereof.

104. 104. The method of any one of claims 66 to 103, wherein the one or more hydrophobic solvents constitute at least 95% of the total solvent concentration in the formulation.

105. 105. The method of any one of claims 66-104, wherein the one or more hydrophobic solvents comprise dichloromethane, chloroform, tetrahydrofuran, toluene, ethyl acetate, hexane, cyclohexane, squalene, squalene, petrolatum, a petrolatum-containing solvent or solvent mixture, petrolatum ointment, a petrolatum-based ointment, or any combination thereof.

106. 106. The method of any one of claims 66 to 105, wherein the one or more hydrophobic solvents comprise petrolatum or petrolatum.

107. 107. The method of any one of claims 66 to 106, wherein the melanin formulation is a sunscreen or sunblock product for application to the skin; and the functionalized artificial melanin material is provided in the formulation to promote skin healing in the event of UV-induced skin damage.

108. The method according to any one of claims 66 to 107, wherein the concentration of the functionalized artificial melanin material in the melanin formulation is selected from the range of 0.5 mg / mL to 100 mg / mL.

109. 109. The method of any one of claims 66 to 108, wherein the melanin preparation is characterized by a contact angle of at least 90°.

110. The method according to any one of claims 66 to 109, wherein the functionalized artificial melanin nanoparticles dispersed in the melanin formulation are characterized by a zeta potential of -20 mV or greater.

111. 111. The method of any one of claims 66 to 110, wherein the melanin preparation is characterized as a stable colloid.

112. A method for preparing the functionalized artificial melanin material according to any one of claims 1 to 35, comprising: providing non-functionalized artificial melanin nanoparticles; exposing the non-functionalized artificial melanin nanoparticles to a precursor of the modifying agent for a limited time; wherein the exposing step comprises: conjugating the non-functionalized artificial melanin nanoparticles with the precursor, thereby forming functionalized artificial melanin nanoparticles with the modifying agent. A method comprising:

113. 1. A method for preparing a functionalized artificial melanin material, comprising: providing non-functionalized artificial melanin nanoparticles; exposing the non-functionalized artificial melanin nanoparticles to a precursor of the modifying agent for a limited time; wherein the exposing step comprises: conjugating the non-functionalized artificial melanin nanoparticles with the precursor, thereby forming functionalized artificial melanin nanoparticles with a modifying agent. wherein the functionalized artificial melanin nanoparticles comprise a surface functionalized with the modifying agent via a linker group; the modifying agent comprises the linker group and a functional group attached to the linker group; The method wherein the linker group is a nucleophilic group.

114. 114. The method of claim 112 or 113, wherein the linker group is an amine group, a thiol group, or any combination thereof.

115. The functionalized artificial melanin material of claim 114, wherein the linker group is an amine group.

116. The method of any one of claims 112 to 115, wherein the non-functionalized artificial melanin nanoparticles are hydrophilic and dispersed in an aqueous solution.

117. 117. The method of any one of claims 112 to 116, wherein the exposing step comprises adding a predetermined amount of the precursor to the aqueous solution having the non-functionalized artificial melanin nanoparticles.

118. 118. The method of any one of claims 112 to 117, wherein the conjugating step comprises rendering the functionalized artificial melanin nanoparticles more hydrophobic than the non-functionalized artificial melanin nanoparticles provided.

119. 119. A method according to any one of claims 112 to 118, comprising extracting said material or functionalised artificial melanin nanoparticles thereof.

120. The method according to any one of claims 112 to 119, comprising a step of aging or oxidizing the non-functionalized artificial melanin nanoparticles to form or increase the content of quinones in the non-functionalized artificial melanin nanoparticles.

121. 121. The method of any one of claims 112 to 120, wherein the providing step comprises preparing the non-functionalized artificial melanin nanoparticles.

122. 122. The method of any one of claims 112 to 121, wherein the conjugating step occurs via a Michael addition or via a Schiff base reaction.

123. 43. The functionalized artificial melanin material according to any one of claims 1 to 42, wherein each of said functionalized artificial melanin material or its functionalized artificial melanin nanoparticles is not bound to, conjugated to, attached to, coated by, encapsulated by, or otherwise chemically associated with a natural or biological proteinaceous matrix, component, or lipid.

124. 124. The functionalized artificial melanin material of any one of claims 1 to 42 and 123, wherein each of the functionalized artificial melanin material or its functionalized artificial melanin nanoparticles is characterized as eumelanin, pheomelanin, allomelanin, or a combination thereof.

125. 125. The functionalized artificial melanin material of any one of claims 1 to 42 and 123 to 124, comprising artificial allomelanin nanoparticles, artificial polydopamine nanoparticles, or any combination thereof.

126. A functionalized artificial melanin material described in any one of claims 1 to 42 and 123 to 125, wherein each of the functionalized artificial melanin materials or functionalized artificial melanin nanoparticles thereof comprises multiple types of melanin oligomers and / or polymers; and each melanin oligomer and / or polymer comprises multiple covalently bonded melanin building blocks.

127. 127. The functionalized artificial melanin material of claim 126, wherein the melanin basic unit comprises one or more substituted or unsubstituted catechol-based monomer units, substituted or unsubstituted polyol-based monomer units, substituted or unsubstituted phenol-based monomer units, substituted or unsubstituted indole-based monomer units, substituted or unsubstituted benzothiazine-based monomer units, substituted or unsubstituted benzothiazole-based monomer units, substituted or unsubstituted dopamine-based monomer units, or any combination thereof.

128. A functionalized artificial melanin material according to any one of claims 1 to 42 and 123 to 127, comprising artificial allomelanin nanoparticles.

129. 129. The functionalized artificial melanin material of any one of claims 1 to 42 and 123 to 128, comprising solid or non-porous artificial allomelanin nanoparticles, walnut artificial allomelanin nanoparticles, hollow artificial allomelanin nanoparticles, lacy artificial allomelanin nanoparticles, or combinations thereof.

130. A functionalized artificial melanin material described in any one of claims 1 to 42 and 123 to 126, wherein at least a portion of the melanin building blocks each independently comprise substituted or unsubstituted naphthalene.

131. A functionalized artificial melanin material described in any one of claims 1 to 42 and 123 to 126, wherein at least a portion of the melanin basic units each independently comprise dihydroxynaphthalene.

132. 132. The functionalized artificial melanin material of any one of claims 1 to 42, 123 to 126 and 131, wherein at least a portion of the artificial melanin material comprises nitrogen-free melanin oligomers.

133. A functionalized artificial melanin material according to any one of claims 1 to 42, 123 to 126 and 131 to 132, wherein at least a portion of the artificial melanin material comprises polydopamine.

134. 134. The functionalized artificial melanin material of any one of claims 1 to 42, 123 to 126, and 131 to 133, wherein at least a portion of the melanin building blocks each independently comprise a substituted or unsubstituted dopamine monomer.

135. The functionalized artificial melanin material according to any one of claims 1 to 42, 123 to 126, and 131 to 134, wherein at least a portion of the melanin basic units are independently selected from the group consisting of substituted or unsubstituted dihydroxydopamine monomer units, substituted or unsubstituted dioxydopamine monomer units, substituted or unsubstituted dihydroxynaphthalene monomer units, substituted or unsubstituted dihydroxyphenylalanine monomer units, substituted or unsubstituted dioxydopamine monomer units, substituted or unsubstituted tyrosine monomer units, substituted or unsubstituted tyramine monomer units, any derivatives thereof, and any combinations thereof.

136. The functionalized artificial melanin material according to any one of claims 1 to 42, 123 to 126, and 131 to 134, wherein at least a portion of the melanin basic units are each independently selected from the group consisting of 3,4-dihydroxydopamine monomer units, 3,4-dioxydopamine monomer units, 3,4-dihydroxynaphthalene monomer units, 1,8-dihydroxynaphthalene, 1-3,4-dihydroxyphenylalanine monomer units, and any combination thereof.

137. 137. The functionalized artificial melanin material of any one of claims 126 to 136, wherein at least 50% of the plurality of melanin oligomers are selected from the group consisting of monomer units, dimers, trimers, tetramers, pentamers, and any combination thereof.

138. A functionalized artificial melanin material described in any one of claims 126 to 137, wherein each melanin oligomer is non-covalently associated with at least one other melanin oligomer or melanin monomer through at least one of hydrogen bonding and π-π stacking of naphthalene rings; and the melanin monomer comprises the melanin basic unit.

139. The artificial melanin material comprises a porous artificial melanin material; the melanin oligomers and / or polymers of the porous artificial melanin material are arranged to form an internal structure having a plurality of pores; and the porous artificial melanin material has a thickness of 0.1 cm ３ 139. The functionalized artificial melanin material of any one of claims 1-42 and 123-138, characterized by a pore volume per mass of material of 0.5 nm or greater, and at least a portion of the pores having at least one size dimension of 0.5 nm or greater.

140. The functionalized artificial melanin material of any one of claims 1 to 42 and 123 to 139, wherein the artificial melanin material comprises artificial melanin particles; and at least some of the artificial melanin particles are solid particles, hollow particles, lacy particles, or any combination thereof.

141. A functionalized artificial melanin material described in any one of claims 1 to 42 and 123 to 126, wherein at least a portion of the artificial melanin material comprises one or more selenomelanine polymers; the one or more selenomelanine polymers comprise a plurality of covalently bonded selenomelanine building blocks; and the chemical formula of each of the one or more selenomelanine building blocks includes at least one selenium atom.

142. 142. The method of claim 141, wherein each selenomelanin polymer is a pheomelanin.

143. 143. The method of claim 141 or 142, wherein the chemical formula of each of the one or more selenomelanin building blocks includes at least one covalent bond with each of the at least one selenium atom.

144. 144. The method of any one of claims 141-143, wherein the chemical formula of each of the one or more selenomelanin building blocks comprises substituted or unsubstituted benzoselenazine or a derivative thereof, substituted or unsubstituted benzoselenazole or a derivative thereof, substituted or unsubstituted 7,10-dihydro-2H-[1,4]selenazino[3,2-h]isoquinolin-3(4H)-one or a derivative thereof, substituted or unsubstituted benzoselenazinone or a derivative thereof, or any combination thereof.

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