Infrared emissive conjugated polymers, composites, and compositions

Abstract

The present disclosure pertains to a polymeric composition that includes at least one polymer that features π-conjugation, and where the at least one polymer includes an electron acceptor that includes furan-flanked diketopyrrolopyrrole acceptors and an electron donor. The composition features emission in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof. The present disclosure also pertains to methods of imaging a tissue of a subject by (1) administering a polymeric composition of the present disclosure to the subject; (2) applying a light source to the subject; and (3) detecting emitted light from the light source, where the emitted light is generated by interactions between the light source and the polymeric composition.

Description

TITLEINFRARED EMISSIVE CONJUGATED POLYMERS, COMPOSITES, AND COMPOSITIONSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 657,016, filed on June 6, 2024. The entirety of the aforementioned application is incorporated herein by reference.BACKGROUND

[0002] A need exists for improved polymeric compositions with high fidelity imaging properties. Numerous embodiments of the present disclosure aim to address the aforementioned need.SUMMARY

[0003] In some embodiments, the present disclosure pertains to a polymeric composition. In some embodiments, the polymeric composition includes at least one polymer that features n- conjugation. In some embodiments, the polymeric composition includes a plurality of polymers that each feature ^-conjugation. In some embodiments, the polymers include an electron acceptor and an electron donor. In some embodiments, the composition features emission in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof.

[0004] Additional embodiments of the present disclosure pertain to methods of imaging a tissue of a subject. Such methods generally include: (1) administering a polymeric composition of the present disclosure to the subject; (2) applying a light source to the subject; and (3) detecting emitted light from the light source, where the emitted light is generated by interactions between the light source and the polymeric composition.DRAWINGS

[0005] FIG. 1 shows the identity of conjugated polymers P1-P6, utilized in various embodiments of the present disclosure.

[0006] FIG. 2 shows the gel permeation chromatography (GPC) analysis of P5, proving that it is a polymer.

[0007] FIGS. 3A-3B show graphical representations of the UV-Vis absorption spectrum (FIG. 3A) and the infrared emission spectrum of polymers P2, P4 and P6 (FIG. 3B).

[0008] FIGS. 4A-4C show the graphical representation of nanoparticles processed from polymers P1-P6 (FIGS. 4A-4B), and the size distribution and stability measurements of nanoparticles derived from polymers P1-P6 (FIG. 4C).

[0009] FIGS. 5A-5D show the emission spectra of P2 and P6 under different conditions, indicating that P2 and P5 demonstrate near infrared emission (NIR).

[0010] FIG. 6 demonstrates the long term colloidal stability of nanoparticles derived from Pl, P2, P3, and P4 over a timespan of one week as measured by dynamic light scattering in water.

[0011] FIG. 7 shows infrared emission stability over time of nanoparticles derived from P1-P6 compared to ICG.

[0012] FIG. 8 shows an infrared image of (left) ICG compared to (right) nanoparticles derived from P6.

[0013] FIG. 9 shows the in vivo imaging results of a mouse injected with P6-containing nanoparticles, displaying NIR emission.DETAILED DESCRIPTION[00141 It is to be understood that both the foregoing general description and the following detailed description are illustrative and explanatory, and are not restrictive of the subject matter, as claimed. In this application, the use of the singular includes the plural, the word “a” or “an” means “at least one”, and the use of “or” means “and / or”, unless specifically stated otherwise. Furthermore, the use of the term “including”, as well as other forms, such as “includes” and “included”, is not limiting. Also, terms such as “element” or “component” encompass both elements or components that include one unit and elements or components that include more than one unit unless specifically stated otherwise.

[0015] The section headings used herein are for organizational purposes and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including, but not limited to, patents, patent applications, articles, books, and treatises, are hereby expressly incorporated herein by reference in their entirety for any purpose. In the event that one or more of the incorporated literature and similar materials defines a term in a manner that contradicts the definition of that term in this application, this application controls.

[0016] Fluorescence imaging has emerged as a powerful tool for visualizing biological targets (biochemical processes, organelles, and organs) for both fundamental research and clinical applications. While optical imaging in the visible (400-700 nm) and traditional near-infrared (NIR-I, 700-900 nm) are routine, investigations probing farther into the second near-infrared window (NIR-II, 1000-1700 nm) have distinct advantages, including (1) minimal interfering photon scattering or tissue autofluorescence, (2) deep tissue penetration depth (~ 10 mm), and (3) high spatial resolution.

[0017] As such, imaging materials featuring NIR-II emission have been investigated for guiding surgical resections and biopsies in real-time, lymph node mapping, photoacoustic tomography, photothermal therapy, and drug delivery, among other applications. While various classes of organic fluorophores have been reported which feature NIR emission and biocompatibility, few simultaneously display significant emission in the NIR-II, high quantum yields (QY), and large extinction coefficients, thereby limiting their clinical potential.

[0018] Organic imaging agents have been targeted due to their greater potential for biocompatibility as compared to inorganics-an important prerequisite for in vivo applications. The first (and one of the only) clinically approved IR-emitting dyes is the small-molecule indocyanine green (ICG), which has been utilized since the 1950s for medical diagnostics. ICG is applied as an imaging agent for diverse medical technologies. For example, ICG is currently used for intraoperative assessment of tumor extent and real-time differentiation between tumor-involved and tumor-free tissue to enhance resection margins. However, ICG has limited utility as it displays virtually no emission beyond 900 nm, is relatively unstable, displays non-specific binding to proteins, lacks tumor specificity, and has a low quantum yield of 2.5%.

[0019] Conjugated polymers (CPs) represent an alternative class of organic chromophore that have recently been investigated due to their high extinction coefficient, large Stokes shift, photo stability, and biocompatibility. Recent reports have demonstrated NIR-II emitting CPs as either nanoparticles isolated in solution, or encapsulated within polymeric surfactants (CPNs). While these functional polymer nanoparticles have proven efficacious for targeted imaging for a broad spectrum of disorders and diseases, their limited QY has delayed their widespread adoption for diagnostics and intra-operative applications.

[0020] The brightness of a NIR-II emitting chromophore is proportional to the product of the QY and the extinction coefficient (s) at the excitation wavelength. Therefore, CPs are theoretically advantageous as their K-cxtcndcd topology offers larger mass-normalized s than what can be realized with organic small-molecule or inorganic alternatives. Furthermore, the band-structure of CPs can be systematically adjusted using well established molecular engineering tools to rationally afford NIR-II absorption and emission, which is typically enabled through narrowing the band-gap using an alternating donor-acceptor (D-A) backbone architecture. For example, significant backbone engineering efforts have demonstrated that indacenodithieno[3,2- b]thiophene-based (PTQ; Aem,max = ~ 1057 nm), furan-containing diketopyrrolopyrrole-based (PDFT; Aem.max = ~ 1032 nm), and benzodithiophene-based (PBTQ; A.em,max = ~ 950 nm) D-A CPNs feature emission in the NIR-II, among others.

[0021] However, the same tools to achieve efficient light harvesting in the NIR results in highly planar structures that typically aggregate, particularly in the nanoparticle form factor. In this packed morphology, materials feature rotational and vibrational motions that offer non-radiative pathways to dissipate energy and therefore reduce the QY.

[0022] While alternative small molecule based fluorescent imaging agents have avoided this challenge by leveraging aggregation-induced emission (AIE), such AIE luminogens (AIEgens) rarely display strong emission in the NIR-II, and require elaborate multistep procedures to incorporate handles for cell labeling.

[0023] Despite advantages, a vast number of reports indicate that NIR-emitting CPNs either do not have emission extending into the NIR-II or the brightness required for high fidelity imaging. As such, a need exists for CP-bascd materials featuring high performance optical properties while also featuring easily tunable handles for cell labeling. Such CP-based materials would be uniquely poised to tackle the diverse set of problems associated with in vivo imaging and image guided surgeries. Numerous embodiments of the present disclosure aim to address the aforementioned need.

[0024] Polymeric compositions[00251 In some embodiments, the present disclosure pertains to a polymeric composition. In some embodiments, the polymeric composition includes at least one polymer that features n- conjugation. In some embodiments, the polymeric composition includes a plurality of polymers that each feature 7r-conjugation. In some embodiments, the polymers include an electron acceptor and an electron donor. In some embodiments, the composition features emission in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof. As set forth in more detail herein, the polymeric compositions of the present disclosure can include numerous embodiments.

[0026] Polymers

[0027] The polymeric compositions of the present disclosure can include various polymers. For instance, in some embodiments, the polymers include, without limitation, copolymers, statistical copolymers, block copolymers, or combinations thereof. In some embodiments, the polymers include copolymers with varying functionalized R groups. In some embodiments, the polymers include polymers of varying sizes.

[0028] In some embodiments, the polymers include statistical copolymers. In some embodiments, the electron donors are randomly distributed along the polymer backbone of the statistical copolymers.

[0029] In some embodiments, the polymers include block copolymers. In some embodiments, the block copolymers include repeat units of electron acceptors and electron donors. In some embodiments, the block copolymers are covalently linked to one or more additional blocks that include an electron donor, an electron acceptor, a non-conjugated polymer, or combinations thereof.

[0030] In some embodiments, the polymer may further include side chains on the donor or acceptor units. In some embodiments, the side chains independently include, without limitation, alkyls, Ci-Css alkyl, aryls, C6-C20 aryls, heteroaryls, C3-C20 heteroaryls, or combinations thereof.

[0031] Electron acceptors

[0032] The polymers of the present disclosure may include various electron acceptors. For instance, in some embodiments, the electron acceptors include, without limitation, arenes, heteroarenes, unsaturated linkers, furan-flanked diketopyrrolopyrrole acceptors, or combinations thereof. In some embodiments, the electron acceptors include furan-flanked diketopyrrolopyrrole acceptors. In some embodiments, each polymer in a composition of the present disclosure includes a furan-flanked diketopyrrolopyrrole acceptor.

[0033] Electron donors

[0034] The polymers of the present disclosure can include various electron donors. For instance, in some embodiments, the electron donors include, without limitation, unsubstituted or substituted thiophene, furan, pyrrole, selenophene, benzene, naphthalene, fluorene, carbazole, phenothiazine, phenoxazine, benzodithiophene, indole, indolocarbazole, thieno[3,2-b]thiophene, dithieno[3,2- b:2',3'-d]thiophene, bithiophene, 3, 3 ’-bithiophene, substituted aryl or heteroaryl units that include one or more nitrogen, oxygen, or sulfur atoms, or combinations thereof.

[0035] In some embodiments, the electron donors include, without limitation, thiophene, thieno [3, 2-b] thiophene, 3,3’ -bithiophene, or combinations thereof. In some embodiments, the electron donors are substituted with one or more groups that independently include alkyl, alkoxy, aryl, heteroaryl, cyano, halogen, or amino groups.

[0036] Polymer structures

[0037] The polymers of the present disclosure can include various structures. For instance, in some embodiments, the polymers include one or more of the following structures:, or combinations thereof.

[0038] In some embodiments, the polymers include the following structure:

[0039] In some embodiments, the polymers include the following structure:

[0040] In some embodiments, each of Ri and R2 independently includes, without limitation, linear alkyls, branched alkyls, linear or branched Ci-C > alkyls, cycloalkyls, alkenyls, alkynyls, aryls, C6-C20 aryls, heteroaryls, C3-C20 heteroaryls, alkoxy groups, halogens, hydrocarbylene groups, hydrocarbyl groups, hydrocarbylene-aryl-hydrocarbyl groups, polyether-containing groups, cyano (CN), hydroxyl ( — OH), thioether ( — SR), ether ( — OR), carboxyl ( — COOH), ester ( — COOR), amino ( — NH2), monoalkylamino ( — NHR3), dialkylamino ( — NR3R4), or combinations thereof.

[0041] In some embodiments, at least one of Ri and R2 includes hydrocarbylene-aryl-hydrocarbyl groups. In some embodiments, the hydrocarbylene and hydrocarbyl group each independently includes Co-Cse. In some embodiments, the aryl group includes C6-C20.

[0042] In some embodiments, at least one of Ri and R2 includes polyether-containing groups. In some embodiments, the polyether-containing groups include linear or branched alkyl chains substituted with poly(ethylene glycol) (PEG), polypropylene glycol) (PPG), or combinations thereof. In some embodiments, the polyether-containing groups include 1 to 100 repeating units.

[0043] In some embodiments, at least one of Ri and R2 includes a halogen. In some embodiments, the halogen includes, without limitation, F, Cl, Br, I, or combinations thereof.

[0044] In some embodiments, at least one of Ri and R2 includes a monoalkylamino ( — NHR3), dialkylamino ( — NR3R4), or combinations thereof. In some embodiments, each of R3 and R4 independently includes a C1-C24 hydrocarbyl.

[0045] In some embodiments, each of Ri and R2 independently includes linear alkyls. In some embodiments, the linear alkyls include C16H33.

[0046] In some embodiments, each of Ri and R2 independently includes branched alkyls. In some embodiments, the branched alkyls include a first branch and a second branch. In some embodiments, the first branch includes C10H21 and the second branch includes CsHn.

[0047] In some embodiments, each of R3 and R4 independently includes, without limitation, an alkyl group, linear alkyls, branched alkyls, linear or branched Ci-Cse alkyls, cycloalkyls, alkenyls, alkynyls, aryls, C6-C20 aryls, heteroaryls, C3-C20 heteroaryls, alkoxy groups, halogens, hydrocarbylene groups, hydrocarbyl groups, hydrocarbylene-aryl-hydrocarbyl groups, polyether- containing groups, cyano (CN), hydroxyl ( — OH), thioether ( — SR), ether ( — OR), carboxyl ( — COOH), ester ( — COOR), or combinations thereof. In some embodiments, each of R3 and R4 independently includes an alkyl group.

[0048] In some embodiments, at least one of R3 and R4 includes hydrocarbylene-aryl-hydrocarbyl groups. In some embodiments, the hydrocarbylene and hydrocarbyl group each independently includes Co-Cv>. In some embodiments, the aryl group includes C6-C20. In some embodiments, each of R3 and R4 independently includes a C1-C24 hydrocarbyl.

[0049] In some embodiments, at least one of R3 and R4 includes polyether-containing groups. In some embodiments, the polyether-containing groups include linear or branched alkyl chains substituted with poly(ethylene glycol) (PEG), poly (propylene glycol) (PPG), or combinations thereof. In some embodiments, the polyether-containing groups include 1 to 100 repeating units.

[0050] In some embodiments, at least one of R3 and R4 includes a halogen. In some embodiments, the halogen includes, without limitation, F, Cl, Br, I, or combinations thereof.

[0051] In some embodiments, each of R3 and R4 independently includes linear alkyls. In some embodiments, the linear alkyls include C16H33.

[0052] In some embodiments, each of R3 and R4 independently includes branched alkyls. In some embodiments, the branched alkyls include a first branch and a second branch. In some embodiments, the first branch includes C10H21 and the second branch includes CsH 17.

[0053] In some embodiments, each of n and m is an integer of 1 or more. In some embodiments, each of n and m is an integer between 5 and 1,000. In some embodiments, n includes the electron donor.

[0054] In some embodiments, the electron donor in z includes, without limitation, unsubstituted or substituted thiophene, furan, pyrrole, selenophene, benzene, naphthalene, fluorene, carbazole, phenothiazine, phenoxazine, benzodithiophene, indole, indolocarbazole, thieno[3,2-b]thiophene, dithieno[3,2-b:2',3'-d]thiophene, bithiophene, 3,3 ’-bithiophene, substituted aryl or heteroaryl units that include one or more nitrogen, oxygen, or sulfur atoms, or combinations thereof. In some embodiments, the electron donor in z includes, without limitation, thiophene, thieno[3,2- b]thiophene, 3, 3 ’-bithiophene, or combinations thereof.

[0055] In some embodiments, the electron donor in z is substituted with one or more groups. In some embodiments, the groups include, without limitation, alkyl, alkoxy, aryl, heteroaryl, cyano, halogen, amino groups, or combinations thereof.

[0056] In some embodiments, the polymers include one or more of the polymers disclosed in FIG. 1. In some embodiments, the polymers include one or more of Pl, P2, P3, P4, P5, P6, or combinations thereof.

[0057] In some embodiments, the polymers include Pl. In such embodiments, Ri and R each include C16H33 and z includes thiophene.

[0058] In some embodiments, the polymers include P2. In such embodiments, Ri and R2 each include a double-branched alkyl, where the first branch includes C10H21 and the second branch includes CsH 17. In such embodiments, z includes thiophene.

[0059] In some embodiments, the polymers include P3. In such embodiments, Ri and Ri each include C16H33 and z includes 2,2’ -bithiophene.

[0060] In some embodiments, the polymers include P4. In such embodiments, Ri and R2 each include a double-branched alkyl, where the first branch includes C10H21 and the second branch includes Cd lr / . In such embodiments, z includes 2,2’-bithiophene.

[0061] In some embodiments, the polymers include P5. In such embodiments, Ri and R2 each include C16H33 and z includes thieno[3,2-b]thiophene.

[0062] In some embodiments, the polymers include P6. In such embodiments, Ri and Ri each include a double-branched alkyl where the first branch includes C10H21 and the second branch includes CsHn. In such embodiments, z includes thieno[3,2-b]thiophene.

[0063] Polymer molecular weights and degrees of polymerization

[0064] The polymers of the present disclosure can include various molecular weights. For instance, in some embodiments, the polymers of the present disclosure exhibit a number-average molecular weight (Mn) between 3,000 and 200,000 g / mol. In some embodiments, the polymers of the present disclosure exhibit a weight-average molecular weight (Mw) between about 10,000 and 500,000 g / mol.

[0065] The polymers of the present disclosure can include various degrees of polymerization. For instance, in some embodiments, the degree of polymerization may range from 5 to 1,000 repeat units depending on the desired solubility, film-forming properties, and emissive performance.

[0066] Polymer synthesis

[0067] The polymers of the present disclosure may be synthesized in various manners. For instance, in some embodiments, the polymers of the present disclosure may be synthesized via a cross-coupling polymerization method, such as Stille coupling, Suzuki-Miyaura coupling, direct arylation polymerization, or combinations thereof. In some embodiments, the polymerization involves a furan-flanked diketopyrrolopyrrole monomer functionalized with halide or stannyl groups and one or more donor monomers similarly functionalized to enable cross-coupling. In some embodiments, reaction conditions may include a palladium catalyst, an inert atmosphere, and temperatures between 60 °C and 150 °C in organic solvents such as toluene, chlorobenzene, or N-methylpyrrolidone. Post-polymerization workup may include precipitation, Soxhlet extraction, chromatography, or combinations thereof.

[0068] In some embodiments, the polymeric compositions of the present disclosure may be soluble in organic solvents, such as chloroform, toluene, chlorobenzene, and / or tetrahydrofuran. In some embodiments, solubilization in aqueous media may be achieved by incorporating hydrophilic or ionic side chains. In some embodiments, the polymeric compositions of the present disclosure may be processed or used in solution form for inkjet printing, coating, or biological applications.

[0069] Emission properties

[0070] The polymeric compositions of the present disclosure can have various emission properties. For instance, in some embodiments, the polymeric compositions feature emission at wavelengths ranging from 650 nm to 1,700 nm. In some embodiments, the polymeric compositions feature emission in the NIR-I emitting region ranging from 650 nm to 950 nm. In some embodiments, the polymeric compositions feature emission in the NIR- II emitting region ranging from 1,000 nm to 1,350 nm. In some embodiments, the polymeric compositions feature emission in the N1R- Ilb / SWIR emitting region ranging from 1,350 nm to 1,700 nm.

[0071] In some embodiments, the polymers of the present disclosure exhibit quantum yields greater than 0.01 (e.g., in solution, film, or nanoparticle form). In some embodiments, the polymers of the present disclosure exhibit photostability under ambient, thermal, or physiological conditions. In some embodiments, the polymers of the present disclosure exhibit emission lifetimes ranging from nanoseconds to seconds, including phosphorescence or delayed emission. In some embodiments, the polymers of the present disclosure exhibit thermally activated delayed fluorescence (TADF). In some embodiments, reverse intersystem crossing in the polymers of the present disclosure enables efficient NIR emission via triplet harvesting.

[0072] In some embodiments, the polymers of the present disclosure exhibit afterglow emission with long-lived excited states persisting beyond excitation. In some embodiments, such afterglow emissions are useful for background-free imaging and low-dose diagnostics.

[0073] In some embodiments, the polymers of the present disclosure exhibit mechanoluminescence or sonochemical activation. In some embodiments, emission is triggered or enhanced by external stimuli, such as ultrasound, mechanical force, or pressure.

[0074] In some embodiments, the polymers of the present disclosure exhibit reactive oxygen species (ROS)-responsive emission. In some embodiments, oxidation induces or modulates emission for sensing or therapeutic feedback.

[0075] In some embodiments, the polymers of the present disclosure exhibit the aforementioned optical behaviors in various forms, such as in solution, film, or particulate form. In some embodiments, the polymers of the present disclosure may be modulated further by environmental parameters, such as temperature, polarity, pH, redox state, and mechanical input.

[0076] Forms

[0077] The polymeric compositions of the present disclosure may be in various forms. For instance, in some embodiments, the composition is in a form that includes, without limitation, films, coatings, particles, composite materials, or combinations thereof.

[0078] In some embodiments, the polymeric compositions of the present disclosure are in the form of a particle. In some embodiments, the emission intensity, lifetime, and wavelength of the polymeric compositions may be further influenced by encapsulation, aggregation state, or the surrounding dielectric environment of the particle.

[0079] In some embodiments, the particles of the present disclosure may further include a surfactant. In some embodiments, the particle is functionalized with a ligand for cell or tissue labeling.

[0080] The particles of the present disclosure may be in various forms. For instance, in some embodiments, the particles of the present disclosure may be in the form of nanoparticles, microparticles, submicron particles, micelles, vesicles, or combinations thereof. In some embodiments, the particles of the present disclosure may be in the form of nanoparticles. In some embodiments, the particles of the present disclosure may be in the form of microparticles.

[0081] The particles of the present disclosure may have various sizes. For instance, in some embodiments, the particles of the present disclosure have sizes that range from about 10 nm to about 10 pm. In some embodiments, the particles of the present disclosure have sizes that range from about 10 nm to about 1 pm. In some embodiments, the particles of the present disclosure have sizes that range from about 10 nm to about 500 nm. In some embodiments, the particles of the present disclosure have sizes that range from about 10 nm to about 100 nm.

[0082] The polymers of the present disclosure may be formulated into particles (e.g., nanoparticles, microparticles, submicron particles, micelles, and / or vesicles) using various methods. Such methods may include, without limitation, nanoprecipitation, reprecipitation, emulsion processing, dialysis, self-assembly via solvent exchange, or combinations thereof.

[0083] In some embodiments, the polymers of the present disclosure may be formulated into particles through the utilization of stabilizing agents. In some embodiments, the stabilizing agents impart stability, functionality, and / or targeting capability. Suitable stabilizers and coatings include, without limitation, surfactants (e.g., ionic, nonionic, and / or zwitterionic surfactants), polymers (e.g., amphiphilic and / or block copolymers, such as, Pluronics, proteins or peptides (e.g., albumin, transferrin, and / or antibodies), ionic liquids, polysaccharides (e.g., dextran and / or chitosan), synthetic or biomimetic ligands, polyelectrolyte multilayers, lipid bilayers, or combinations thereof. In some embodiments, the stabilizing agents may provide colloidal stability, biocompatibility, targeting, or charge modulation in aqueous or biological environments.

[0084] In some embodiments, the polymeric compositions of the present disclosure are in the form of a film or coating. Various methods may be utilized to form such films or coatings. For instance, in some embodiments, polymers may be dissolved in organic solvents (e.g., toluene, chlorobenzene, and / or THF) or aqueous media (e.g., with solubilizing side chains and / or additives) to form stable solutions. These solutions may then be deposited onto substrates to form films, coatings, or device layers using techniques such as spin-coating, blade coating, doctor blading, drop-casting, slot-die coating, spray coating, inkjet printing, screen printing, and / or dip-coating.

[0085] The polymeric compositions of the present disclosure may be deposited onto various substrates to form films or coatings. For instance, in some embodiments, the substrates may include, without limitation, glass, silicon, flexible polymers, paper, textiles, biological tissues, or combinations thereof. In some embodiments, the substrates may be further processed by thermal annealing or solvent vapor annealing to optimize crystallinity, morphology, or optoelectronic behavior.

[0086] Films or coatings of the present disclosure may have various thicknesses. For instance, in some embodiments, the films and coatings of the present disclosure may range in thickness from 5 nm to 5 pm. In some embodiments, the films and coatings of the present disclosure may range in thickness from 5 nm to 500 nm. In some embodiments, the films and coatings of the present disclosure may range in thickness from 5 nm to 100 nm.

[0087] In some embodiments, the polymeric compositions of the present disclosure are in the form of a composite material. In some embodiments, the composite materials may be in the form of a blended formulation that includes other organic or inorganic materials. In some embodiments, the composite materials may include, without limitation, morphology -directing agents, optoelectronic modifiers, photosensitizers, sonosensitizers, nanoparticles, dyes, contrast agents, electron or energy acceptors, or combinations thereof.

[0088] In some embodiments, the composite materials of the present disclosure may include morphology-directing agents. In some embodiments, the morphology-directing agents include, without limitation, block copolymers, surfactants, amphiphilic additives that promote nanophase separation or control polymer packing, or combinations thereof.

[0089] In some embodiments, the composite materials of the present disclosure may include optoelectronic modifiers. In some embodiments, the optoelectronic modifiers include, without limitation, small-molecule chromophores, oligomers, co-polymers that modulate emission wavelength, brightness, lifetime through energy transfer or charge modulation, or combinations thereof.

[0090] In some embodiments, the composite materials of the present disclosure may include photosensitizers or sonosensitizers. In some embodiments, the photosensitizers or sonosensitizers facilitate generation of reactive oxygen species (ROS) upon light or ultrasound activation, thereby enabling applications in photodynamic therapy, sonodynamic therapy, or stimuli-responsive imaging.

[0091] In some embodiments, the composite materials of the present disclosure may include nanoparticles, dyes, or contrast agents. In some embodiments, the nanoparticles, dyes, or contrast agents include, without limitation, SPIONs, gold nanoparticles, iodine, and / or Gd-complexes. In some embodiments, the nanoparticles, dyes, or contrast agents enable multimodal imaging, including magnetic, radiologic, and acoustic modalities.

[0092] In some embodiments, the composite materials of the present disclosure may include electron or energy acceptors. In some embodiments, the electron or energy acceptors, include, without limitation, quenchers, fluorescence resonance energy transfer (FRET) pairs, scavengers to investigate or modulate photophysical behaviors, or combinations thereof.

[0093] The aforementioned additives may be blended with the composites of the present disclosure in various manners. For instance, in some embodiments, the aforementioned additives may be physically blended, co-encapsulated, co-polymerized, or covalently tethered to a polymer backbone or side chain. In some embodiments, composites are formed via co-precipitation, layer- by-layer assembly, emulsion blending, or post-fabrication loading.

[0094] The incorporation of the aforementioned additives to the composites of the present disclosure may modulate a polymer’s property in various manners. For instance, in some embodiments, the aforementioned additives may affect self-assembly behavior, film morphology or crystallinity, emission spectra or quantum yield, lifetime or afterglow persistence, stimuli- responsiveness (e.g., ultrasound, redox, pH, temperature), and / or compatibility with therapeutic or diagnostic platforms.

[0095] Methods of imaging a tissue of a subject

[0096] The polymeric compositions of the present disclosure may have various advantageous applications. For instance, in some embodiments, the polymeric compositions of the present disclosure may be suitable for use as an imaging agent.

[0097] Additional embodiments of the present disclosure pertain to methods of imaging a tissue of a subject. Such methods generally include: (1) administering a polymeric composition of the present disclosure to the subject; (2) applying a light source to the subject; and (3) detecting emitted light from the light source, where the emitted light is generated by interactions between the light source and the polymeric composition. As set forth in more detail herein, the methods of the present disclosure can have numerous embodiments.

[0098] Administration of polymeric compositions to subjects

[0099] Various methods may be utilized to administer the polymeric compositions of the present disclosure to subjects. For instance, in some embodiments, the administration occurs by a method that includes, without limitation, intravenous administration, subcutaneous administration, transdermal administration, topical administration, intraarterial administration, intrathecal administration, intracranial administration, intraperitoneal administration, intraspinal administration, intranasal administration, intraocular administration, oral administration, intratumor administration, local administration, or combinations thereof. In some embodiments, the administering includes local administration to a specific tissue of a subject. In some embodiments, the tissue includes a tumor.

[0100] Applying a light source

[0101] The methods of the present disclosure may be utilized to apply various light sources to subjects. For instance, in some embodiments, the light source is operable to emit light from the polymeric composition in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof. In some embodiments, the light source includes, without limitation, incident light sources, laser light sources, laser diodes, light emitting diodes, plasma lamps, gas discharge lamps, synchroton light sources, free electron lasers, or combinations thereof.

[0102] Detecting emitted light from the light source

[0103] The methods of the present disclosure may be utilized to detect various types of emitted light from light sources. For instance, in some embodiments, the emitted light includes wavelengths in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof.

[0104] In some embodiments, the emitted light includes emissions at wavelengths ranging from 650 nm to 1,700 nm. In some embodiments, the emitted light includes emissions in the NIR-I emitting region ranging from 650 nm to 950 nm. In some embodiments, the emitted light includes emissions in the NIR-II emitting region ranging from 1,000 nm to 1,350 nm. In some embodiments, emitted light includes emissions in the NIR-IIb / SWIR emitting region ranging from 1,350 nm to 1,700 nm.

[0105] Various methods may be utilized to detect emitted light from light sources. For instance, in some embodiments, the detection includes generating an image of a subject based on the detected emitted light. In some embodiments, the detection includes quantitatively measuring the emitted light source.

[0106] In some embodiments, the detection occurs through the utilization of a detector. In some embodiments, the detector includes, without limitation, a camera, a sensor, photodiodes, charge- coupled devices (CCD), complementary metal-oxide-semiconductor (CMOS) sensors, or combinations thereof.

[0107] Subjects

[0108] The methods and systems of the present disclosure may be utilized to image tissues of various subjects. For instance, in some embodiments, the subject is a human being. In some embodiments, the subject is a non-human mammal.

[0109] Applications

[0110] The methods of the present disclosure may be utilized for various applications. For instance, in some embodiments, the methods of the present disclosure may be used for cancer diagnostics, lymph node mapping, image guided surgeries, bioimaging applications, or combinations thereof.

[0111] Advantages and Applications

[0112] The polymeric compositions of the present disclosure provide several advantages as compared to alternative imaging agents. For instance, in some embodiments, the polymeric compositions of the present disclosure are completely organic and biocompatible. In some embodiments, the emission profiles of the polymeric compositions of the present disclosure extend into the NIR-II. In some embodiments, the structures of the polymeric compositions of the present disclosure are tunable with multiple sites to enhance brightness. In some embodiments, the materials in the polymeric compositions of the present disclosure have long term optical stability. In some embodiments, the materials in the compositions of the present disclosure can be easily functionalized for cell / tissue labeling without impacting optical performance.

[0113] In some embodiments, the polymeric compositions of the present disclosure display enhnaced brightness and photo stability. In some embodiments, infrared emission wavelengths and brightness of the polymeric compositions of the present disclosure can be further modulated by modifying the backbone chemistry, side-chain chemistry, molecular weight, and particle size. In some embodiments, the materials or resultant composites of the polymeric compositions of the present disclosure can be processed by various techniques into different forms to realize multiple applications.

[0114] As such, the polymeric compositions of the present disclosure can have numerous advantageous applications. For instance, in some embodiments, the polymeric compositions of the present disclosure have high potential for utilization in bioimaging technologies and imaging applications, including, but not limited to, cancer diagnostics, lymph node mapping, and image guided surgeries.

[0115] In some embodiments, the polymeric compositions of the present disclosure may be utilized in applications that include, without limitation, biomedical imaging (e.g., in vivo fluorescence imaging, NIR- II imaging, and fluorescence-guided surgery); photodynamic or sonodynamic therapy, where ROS generation may be coupled to polymer emission; wearable or implantable optoelectronic devices; photodetectors and sensors, including environmental or biological sensors based on NIR absorption or emission changes; NIR light-emitting diodes (NIR- OLEDs) and other display technologies; photonic circuits or infrared communications; targeted drug delivery, where optical tracking of polymer-loaded particles is desired; and multimodal diagnostic systems, including polymers co-loaded with MRI, PET, or ultrasound contrast agents.

[0116] In some embodiments, the polymeric compositions of the present disclosure may be utilized in biological applications. In some of such embodiments, the polymeric compositions of the present disclosure may be surface-functionalized for cellular targeting, blood-brain barrier traversal, or tumor accumulation. In some embodiments, the polymeric compositions of the present disclosure may be used in aqueous or physiological media.

[0117] Additional Embodiments

[0118] Reference will now be made to more specific embodiments of the present disclosure and experimental results that provide support for such embodiments. However, Applicant notes that the disclosure below is for illustrative purposes only and is not intended to limit the scope of the claimed subject matter in any way.

[0119] Example 1. Structures and properties of conjugated polymers

[0120] In this Example, Applicant provides new ^-conjugated polymers and corresponding composites with controlled optical emission in the near infrared. Chromophores associated with the polymer composites have tunable optical properties through control of their backbone chemistry, side-chains, molecular weight, and particle size. In particular, Applicant describes in this Example the synthesis, structures and characterizations of the following CPs (conjugated polymers), which have different backbones and side chains: Pl, P2, P3, P4, P5, and P6 (FIG. 1).

[0121] Example 1,1. Synthesis of P5

[0122] This example provides the synthetic procedure for P5. A microwave tube was loaded with 3, 6-bis(5-bromofuran-2-yl)-2,5-dihexadecyl-2,5-dihydropyrrolo[3,4-c]pyrrole- 1,4-dione (143.5 mg, 0.1454 mmol) and 2,5-bis(trimethylstannyl)thieno[3,2-b]thiophene (71.11 mg, 0.1526 mmol). The tube was brought inside the glovebox, and 750 pL of Pd(PPh3)4 / xylenes stock solution (5.0 mol%) was added. The tube was sealed and subjected to the following conditions in a microwave reactor with stirring: 150 °C for 20 min. After this time, the reaction was allowed to cool, leaving a blue solid gelled material.

[0123] The mixture was precipitated into methanol and collected via filtration. The residual solid was loaded into an extraction thimble and washed successively with methanol (2 h), acetone (2 h), hexanes (2 h), and then acetone (2 h). The polymer was dried in vacuo to give 82.9 mg (64.6%). Data are as follows: A7n= 6327 Da, Mw =18036 Da, PDI = 2.85. The Gel permeation chromatography (GPC) analysis of P5 established that the product is a polymer (FIG. 2).

[0124] Example 1,2, Emission measurements of P2, P4 and P6

[0125] The emissions of the polymers P2, P4, and P6 in tetrahydrofuran solution were measured. The results are shown in FIGS. 3A-3B, which demonstrate that all of the polymers shows near infrared (NIR) emission.

[0126] Example 1.3. Incorporation of P5 into nanoparticles

[0127] This example demonstrates the processing of P5 into nanoparticles through nanoprecipitation. P5 (1 mg) and DSPE-PEG2000 (9 mg) were dissolved in THF (2 mL), and the solution was then quickly injected into 9 mL DI water under continuous sonication for 3 min (70% amplitude, phase on for 2 sec and phase off for 1 sec) using syringe pump (CHEMYX) at 0.5 mL / min rate (FIGS. 4A-4B). Subsequently, the solution was left to stir overnight. The aqueous solution was then washed three times using a centrifugal filter (Vivaspin 15R) under centrifugation at 3,700 rpm for 10 min. The washed solution was then filtered through a cellulose acetate syringe filter (0.22 pm) to remove impurities and large particles. The remaining THF was removed by rotary evaporation under vacuum at 50 °C.

[0128] Three batches of nanoparticles were produced and combined to increase the final volume of nanoparticles for all characterizations. The resulting nanoparticles featured colloidal stability as measured by zeta potential (-29) and average diameters of 122 nm as measured by dynamic light scattering (FIG. 4C).

[0129] Example 1,4, Emission studies of P2 and P6

[0130] This example demonstrates the near infrared emission of P2 and P6 as polymers in solution (tetrahydrofuran) (FIGS. 5A-5B) and within the nanoparticle form factor in water (FIGS. 5C-5D). The results show that P2 and P6 demonstrate near infrared emission in solution and in nanoparticle forms.

[0131] Example 1,5. Stability of P 1 -P4

[0132] This example demonstrates the long term colloidal stability of nanoparticles derived from Pl, P2, P3, and P4 over a timespan of one week as measured by dynamic light scattering in water (FIG. 6). Photo stability of the P1-P4 were measured in aqueous buffer against indocyanine green (ICG) under continuous 808 nm radiation for 120 min. EI0 represents the ratio of the fluorescence intensity of the samples relative to the initial NIR fluorescence intensity (FIG. 7).

[0133] Example 1,6. Use of P6 for in vivo imaging

[0134] This example demonstrates the effective use of P6 in vivo using a commercial infrared imager. A CD-I mouse was obtained from Charles River Laboratories and used at ten- weeks-old. The mouse was injected with 200 pL of P6 CPN through the jugular vein for the imaging study. NIR fluorescence imaging was performed using an IR VIVO whole animal imaging system (Photon Etc., Canada) with excitation at 808 nm. Using a long-pass 1250 nm filter, nanoparticles of P6 feature significantly more NIR emission under the imager than commercial ICG (FIG. 8), and strong emission in vivo (FIG. 9).

[0135] Without further elaboration, it is believed that one skilled in the art can, using the description herein, utilize the present disclosure to its fullest extent. The embodiments described herein are to be construed as illustrative and not as constraining the remainder of the disclosure in any way whatsoever. While the embodiments have been shown and described, many variations and modifications thereof can be made by one skilled in the ail without departing from the spirit and teachings of the invention. Accordingly, the scope of protection is not limited by the description set out above, but is only limited by the claims, including all equivalents of the subject matter of the claims. The disclosures of all patents, patent applications and publications cited herein are hereby incorporated herein by reference, to the extent that they provide procedural or other details consistent with and supplementary to those set forth herein.

Claims

WHAT IS CLAIMED IS:

1. A polymeric composition comprising at least one polymer that features ^-conjugation, wherein the at least one polymer comprises an electron acceptor comprising furan-flanked diketopyrrolopyrrole acceptors and an electron donor, and wherein the composition features emission in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof.

2. The polymeric composition of claim 1, wherein the at least one polymer comprises a statistical copolymer, wherein the electron donors arc randomly distributed along the polymer backbone.

3. The polymeric composition of claim 1, wherein the at least one polymer comprises a block copolymer, wherein the block copolymer comprises repeat units of electron acceptors and electron donors.

4. The polymeric composition of claim 1, wherein the at least one polymer comprises:4823-4406-5785V.3 13368-42wherein each of Ri and R2 is independently selected from the group consisting of linear alkyls, branched alkyls, linear or branched Ci-Cw alkyls, cycloalkyls, alkenyls, alkynyls, aryls, C6-C20 aryls, heteroaryls, C3-C20 heteroaryls, alkoxy groups, halogens, hydrocarbylene groups, hydrocarbyl groups, hydrocarbylene-aryl-hydrocarbyl groups, polyether-containing groups, cyano, hydroxyl, thioether, ether, carboxyl ( — COOH), ester, amino ( — NEL), monoalkylamino ( — NHR3), dialkylamino ( — NR3R4), or combinations thereof, wherein each of R3 and R4 is independently selected from the group consisting of an alkyl group, linear alkyls, branched alkyls, linear or branched Ci-Cse alkyls, cycloalkyls, alkenyls, alkynyls, aryls, C6-C20 aryls, heteroaryls, C3-C20 heteroaryls, alkoxy groups, halogens, hydrocarbylene groups, hydrocarbyl groups, hydrocarbylene-aryl-hydrocarbyl groups, polyether- containing groups, cyano, hydroxyl, thioether, ether, carboxyl ( — COOH), or combinations thereof, wherein each of n and m is an integer of 1 or more, and wherein 71 comprises the electron donor.

5. The polymeric composition of claim 4, wherein each of Ri and R2 independently comprises linear alkyls.

6. The polymeric composition of claim 4, wherein each of Ri and R2 independently comprises branched alkyls.

7. The polymeric composition of claim 4, wherein the electron donor is selected from the group consisting of unsubstituted or substituted thiophene, furan, pyrrole, selenophene, benzene, naphthalene, fluorene, carbazole, phenothiazine, phenoxazine, benzodithiophene, indole, indolocarbazole, thieno[3,2-b]thiophene, dithieno[3,2-b:2',3'-d]thiophene, bithiophene, 3,3’-274823-4406-5785V.3 13368-42bithiophene, substituted aryl or heteroaryl units comprising one or more nitrogen, oxygen, or sulfur atoms, or combinations thereof.

8. The polymeric composition of claim 4, wherein the electron donor is selected from the group consisting of thiophene, thieno [3, 2-b] thiophene, 3,3’-bithiophene, or combinations thereof.

9. The polymeric composition of claim 1, wherein the electron acceptor further comprises arenes, heteroarenes, unsaturated linkers, or combinations thereof.

10. The polymeric composition of claim 1, wherein the composition features emission at wavelengths ranging from 650 nm to 1,700 nm.

11. The polymeric composition of claim 1, wherein the composition features emission in the NIR-I emitting region ranging from 650 nm to 950 nm.

12. The polymeric composition of claim 1, wherein the composition features emission in the NIR-II emitting region ranging from 1,000 nm to 1,350 nm.

13. The polymeric composition of claim 1, wherein the composition features emission in the NIR- Ilb / SWIR emitting region ranging from 1,350 nm to 1,700 nm.

14. The polymeric composition of claim 1, wherein the composition is in a form selected from the group consisting of films, coatings, particles, composite materials, or combinations thereof.

15. The polymeric composition of claim 1, wherein the composition is in the form of a particle.

16. A method of imaging a tissue of a subject, said method comprising:284823-4406-5785V.3 13368-42administering a polymeric composition to the subject, wherein the polymeric composition comprises at least one polymer that features ^-conjugation, wherein the at least one polymer comprises an electron acceptor comprising furan-flanked diketopyrrolopyrrole acceptors and an electron donor, and wherein the composition features emission in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof; applying a light source to the subject; and detecting emitted light from the light source, wherein the emitted light is generated by interactions between the light source and the polymeric composition.

17. The method of claim 16, wherein the administering comprises local administration to a specific tissue of a subject.

18. The method of claim 16, wherein the light source is operable to emit light from the polymeric composition in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof.

19. The method of claim 16, wherein the emitted light comprises wavelengths in the near infrared region (NIR), the short-wave infrared region (SWIR), or combinations thereof.

20. The method of claim 16, wherein the emitted light comprises emissions at wavelengths ranging from 650 nm to 1,700 nm.

21. The method of claim 16, wherein the emitted light comprises emissions in the NIR-I emitting region ranging from 650 nm to 950 nm.294823-4406-5785V.3 13368-4222. The method of claim 16, wherein the emitted light comprises emissions in the NIR-II emitting region ranging from 1,000 nm to 1,350 nm.

23. The method of claim 16, wherein emitted light comprises emissions in the NIR-IIb / SWIR emitting region ranging from 1,350 nm to 1,700 nm.

24. The method of claim 16, wherein the detecting comprises generating an image of the subject based on the detected emitted light.

25. The method of claim 16, wherein the detecting comprises quantitatively measuring the emitted light source.

26. The method of claim 16, wherein the subject is a human being.

27. The method of claim 16, wherein the method is used for cancer diagnostics, lymph node mapping, image guided surgeries, bioimaging applications, or combinations thereof.

28. The method of claim 16, wherein the at least one polymer comprises a statistical copolymer, wherein the electron donors are randomly distributed along the polymer backbone.

29. The method of claim 16, wherein the at least one polymer comprises a block copolymer, wherein the block copolymer comprises repeat units of electron acceptors and electron donors.

30. The method of claim 16, wherein the at least one polymer comprises:304823-4406-5785V.3 13368-42wherein each of Ri and Ri is independently selected from the group consisting of linear alkyls, branched alkyls, lineal’ or branched Ci-Cse alkyls, cycloalkyls, alkenyls, alkynyls, aryls, C6-C20 aryls, heteroaryls, C3-C20 heteroaryls, alkoxy groups, halogens, hydrocarbylene groups, hydrocarbyl groups, hydrocarbylene-aryl-hydrocarbyl groups, polyether-containing groups, cyano, hydroxyl, thioether, ether, carboxyl ( — COOH), ester, amino ( — NHz), monoalkylamino ( — NHRr), dialkylamino ( — NR3R4), or combinations thereof, wherein each of R3 and R4 is independently selected from the group consisting of an alkyl group, linear’ alkyls, branched alkyls, linear or branched C1-C36 alkyls, cycloalkyls, alkenyls, alkynyls, aryls, Ce-Czo aryls, heteroaryls, C3-C20 heteroaryls, alkoxy groups, halogens, hydrocarbylene groups, hydrocarbyl groups, hydrocarbylene-aryl-hydrocarbyl groups, polyether- containing groups, cyano, hydroxyl, thioether, ether, carboxyl ( — COOH), or combinations thereof, wherein each of n and m is an integer of 1 or more, and wherein comprises the electron donor.

31. The method of claim 30, wherein each of Ri and R2 independently comprises linear alkyls.314823-4406-5785V.3 13368-4232. The method of claim 30, wherein each of Ri and R2 independently comprises branched alkyls.

33. The method of claim 30, wherein the electron donor is selected from the group consisting of unsubstituted or substituted thiophene, furan, pyrrole, selenophene, benzene, naphthalene, fluorene, carbazole, phenothiazine, phenoxazine, benzodithiophene, indole, indolocarbazole, thieno [3, 2-b] thiophene, dithieno[3,2-b:2',3'-d]thiophene, bithiophene, 3,3’-bithiophene, substituted aryl or heteroaryl units comprising one or more nitrogen, oxygen, or sulfur atoms, or combinations thereof.

34. The method of claim 30, wherein the electron donor is selected from the group consisting of thiophene, thieno[3,2-b]thiophene, 3,3’-bithiophene, or combinations thereof.

35. The method of claim 16, wherein the electron acceptor further comprises arenes, heteroarenes, unsaturated linkers, or combinations thereof.324823-4406-5785V.3 13368-42

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