Photosensitive molecules, nanoparticles and methods for their preparation

Abstract

The application relates to a photosensitive molecule and nanoparticles. In one aspect, the application provides a photosensitive molecule, which comprises a triphenylamine-benzoselenadiazole structural unit, a 4-oxyl benzophenone structural unit, a dialkyl carbonyl structural unit with a sulfur-containing ketal connecting arm, and a dasatinib structural unit with a terminal hydroxyl hydrogen atom removed, the carbon number of the alkyl being 1-20. In another aspect, the application provides nanoparticles, which are co-assemblies formed by co-assembly of the above-mentioned photosensitive molecule and a JP1-modified amphiphilic carrier. The application also provides a preparation method thereof. The application constructs a nano-drug platform with functions of lesion targeting, photodynamic therapy, ROS-triggered drug release and anti-inflammatory regulation.

Description

Technical Field

[0001] This application belongs to the field of materials chemistry. In particular, this application relates to a photosensitive molecule and nanoparticles; specifically, this application relates to a responsive activated biomaterial for targeted therapy and synergistic intervention of inflammation in choroidal neovascularization. Background Technology

[0002] Choroidal neovascularization (CNV) is a significant pathological feature of various fundus diseases, including age-related macular degeneration and pathological myopia. Abnormal neovascularization can breach the barrier between the choroid and retina, accompanied by exudation, hemorrhage, and fibrosis, ultimately leading to retinal structural damage and a continuous decline in visual function. Currently, CNV is primarily treated with anti-vascular endothelial growth factor (VEGF) drugs and photodynamic therapy (PDT). While VEGF drugs can inhibit neovascularization and reduce vascular leakage, they still have limitations, including limited lesion retention time, inadequate treatment response in some patients, high recurrence rates, and the need for repeated administration. Single-drug therapy mainly inhibits the continuous growth of neovascularization but is insufficient to rapidly remove already formed pathological vessels.

[0003] Photodynamic therapy (PDT) generates reactive oxygen species (ROS) under specific wavelengths of light using photosensitizers, which can locally damage pathological vascular endothelial cells, thereby occluding abnormal vessels and reducing leakage. However, PDT alone may lead to incomplete clearance of pathological vessels and subsequent angiogenesis. Simultaneously, the high levels of ROS generated during PDT can induce local oxidative stress, promote microglial cell activation and the release of inflammatory mediators, further exacerbating the inflammatory response at the lesion site and potentially promoting the reactivation of angiogenesis-related signals, thus limiting the therapeutic effect. Combining PDT with controlled drug release provides a new technical pathway for synergistic intervention in CNV. By coupling photosensitizing molecules with small-molecule drugs through ROS-responsive chemical bonds such as thioketal bonds, basic drug release can be achieved using endogenous ROS at the lesion site, and the ROS generated by PDT further promotes the breaking of responsive bonds, thereby significantly enhancing the on-demand drug release at the lesion site. This design combines the rapid vascular damage mediated by PDT with the sustained anti-angiogenic effect mediated by drugs, while reducing non-specific drug exposure in normal tissues.

[0004] Dasatinib (DAS) is a Src family kinase inhibitor that inhibits Src and its downstream signaling pathways, reducing the proliferation, migration, and tube-forming capacity of vascular endothelial cells, thereby continuously suppressing pathological angiogenesis. Furthermore, dasatinib also possesses anti-inflammatory and oxidative stress-regulating effects, inhibiting abnormal microglial activation and reducing the release of inflammatory mediators. Therefore, linking dasatinib to a photosensitive molecule via a ROS-responsive thioacetal bond enables lesion-specific release of dasatinib upon light irradiation, rapidly occluding pathological vessels while continuously inhibiting angiogenesis and alleviating photodynamic-induced secondary inflammation. Further constructing this multifunctional molecule into a surface-modified targeting peptide nanomaterial improves the water dispersibility and biocompatibility of the hydrophobic molecule, prolongs its in vivo circulation time, and enhances its targeted accumulation and retention capacity in the neovascularization region of CNV lesions. The targeting peptide can also synergistically regulate local inflammatory responses, thereby achieving multiple functions including pathological vessel targeting, photodynamic ablation, ROS-responsive drug release, sustained anti-angiogenesis, and regulation of the inflammatory microenvironment.

[0005] Therefore, constructing a nanomedicine platform that combines lesion targeting, photodynamic therapy, ROS-triggered drug release, and anti-inflammatory regulation functions is expected to solve problems such as incomplete pathological vascular clearance, angiogenesis, aggravated inflammatory response, insufficient lesion targeting, and non-specific drug exposure that exist in single photodynamic therapy or single drug therapy, and provide new technical solutions for the synergistic intervention of CNV. Summary of the Invention

[0006] To solve the above-mentioned technical problems, this application provides the following technical solution: On one hand, this application provides a photosensitive molecule characterized in that it comprises a triphenylamine-benzoselenide diazole structural unit, a 4-oxybenzophenone structural unit, a dialkyl carbonyl structural unit containing a thioketal linker arm, and a dasatinib structural unit with the terminal hydroxyl hydrogen atom removed, wherein the alkyl group has 1-20 carbon atoms.

[0007] Preferably, the alkyl group has 1-10 carbon atoms, more preferably 2-6.

[0008] Preferably, the structure of the photosensitive molecule is as follows: .

[0009] On the other hand, this application provides a method for preparing the above-mentioned photosensitive molecule, wherein the method includes the following steps: Under inert gas protection, 4,4-dimethoxy-4-boronic acid triphenylamine, 4,7-dibromobenzo[c][1,2,5]selenodiazole, a first catalyst, and a first base were added to a first reactor, followed by the addition of a first reaction solvent. The mixture was heated under reflux to obtain the first reaction product. Under inert gas protection, (4-bromophenyl)(4-hydroxyphenyl) methyl ketone, dipinacol boronic acid ester, second catalyst, and second base are added to the second reactor, followed by the addition of the second reaction solvent. The reaction is carried out at a certain temperature to obtain the second reaction product. Under inert gas protection, the first reaction product, the second reaction product, the third catalyst, and the third base are added to the third reactor, and then the third reaction solvent is added. The mixture is heated under reflux to obtain the third reaction product. Under inert gas protection, dasatinib, propane-2,2-dimethylbis(thio)diacetic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-methylmorpholine were dissolved in the fourth reaction solvent and reacted with stirring at room temperature to obtain the fourth reaction product. Under inert gas protection, the third reaction product, the fourth reaction product, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 4-dimethylaminopyridine are added to the fifth reaction solvent, and the reaction is stirred at room temperature to obtain the photosensitive molecule.

[0010] Preferably, the inert gas includes nitrogen, helium, neon, and argon; the first catalyst and the third catalyst include tetratetraphenylphosphine palladium, 1,1'-bis(diphenylphosphine)ferrocene palladium(II) chloride, and 1,1'-bis(diphenylphosphine)ferrocene palladium(II) chloride dichloromethane complex; the first base and the third base are alkali metal carbonates, preferably potassium carbonate and sodium carbonate; the first reaction solvent and the third reaction solvent are a mixture of inorganic and organic solvents, wherein the inorganic solvent includes water, and the organic solvent includes... The organic solvent includes tetrahydrofuran, 1,4-dioxane, toluene, and N,N-dimethylformamide, wherein the volume ratio of the organic solvent to the inorganic solvent is 2:1 to 6:1, preferably 4:1; the second catalyst is a tetratetraphenylphosphine palladium, 1,1'-bis(diphenylphosphine)ferrocene palladium(II) chloride, and a 1,1'-bis(diphenylphosphine)ferrocene palladium(II) chloride dichloromethane complex; the second base includes alkali metal acetate, preferably potassium acetate and sodium acetate; the second reaction solvent includes 1,4-dioxane, N,N - Dimethylformamide, toluene, tetrahydrofuran; The first temperature is 60-120 degrees Celsius, preferably 90 degrees Celsius; the fourth and fifth reaction solvents are organic solvents, including tetrahydrofuran, 1,4-dioxane, toluene, etc. N,N -Dimethylformamide.

[0011] In another aspect, this application provides a nanoparticle, wherein the nanoparticle is a co-assembly, and the co-assembly is formed by co-assembling the above-mentioned photosensitive molecule with an amphiphilic carrier modified with JP1.

[0012] Preferably, the JP1-modified amphiphilic carrier is formed by coupling an amphiphilic biomedical polymer material with good biocompatibility with a JP1 peptide that has both angiogenesis targeting and anti-inflammatory activity.

[0013] Preferably, the amphiphilic biomedical polymer material with good biocompatibility, polyethylene glycol-modified phospholipid material (which uses phospholipid as a hydrophobic anchor and PEG as a hydrophilic chain), is preferably DSPE-PEG, more preferably DSPE-PEG2000. The JP1 peptide, which has both angiogenesis targeting and anti-inflammatory activity, is derived from a seven-amino acid fragment optimized from JWA protein and can specifically target integrin αvβ3. At the same time, it exhibits antioxidant, anti-inflammatory and anti-angiogenic effects in the CNV / DR model.

[0014] Preferably, the nanoparticles simultaneously possess multiple functions including lesion targeting, photodynamic therapy, ROS-responsive drug release, and anti-inflammatory regulation.

[0015] In addition, this application provides a method for preparing the above-mentioned nanoparticles, wherein the method includes the following steps: mixing the above-mentioned photosensitive molecule, DSPE-PEG-JP1 (i.e., DSPE-PEG2000-Mal-CFPGSDRFGGGRGD) and DSPE-PEG 2000 The nanoparticles are dissolved in a sixth reaction solvent and slowly added to deionized water under continuous vortex conditions. The mixture is then stirred to remove the sixth reaction solvent, yielding the nanoparticles. The sixth reaction solvent is an organic solvent, including tetrahydrofuran, dimethyl sulfoxide, chloroform, etc.

[0016] Compared with existing technologies, this application constructs a nanomedicine platform that combines lesion targeting, photodynamic therapy, ROS-triggered drug release, and anti-inflammatory regulation. Attached Figure Description

[0017] The present application will now be described with reference to the accompanying drawings, but the application is not limited thereto.

[0018] Figure 1 This is the synthetic route for the TD molecule.

[0019] Figure 2 This is the proton spectrum of the TD molecule.

[0020] Figure 3 High-resolution mass spectrometry characterization of TD molecules.

[0021] Figure 4 The following figures represent the characterization of the TD molecule; Figure a shows the absorption and emission of T in tetrahydrofuran, and Figure b shows the absorption and emission of TD in tetrahydrofuran.

[0022] Figure 5The photodynamic properties of TD molecules were evaluated. Figure a shows the DPBF detection results; Figure b shows the ABDA detection results; Figure c shows the SOSG detection results; and Figure d shows the photostability evaluation results of different nanoparticles.

[0023] Figure 6 The cumulative DAS release curve of TD under 1 mM H2O2 conditions.

[0024] Figure 7 The basic properties of TD@JP1 NPs are characterized; Figure a shows the TEM image and particle size distribution of TD@JP1 NPs; Figure b shows the absorption and emission in water.

[0025] Figure 8 For in vitro cell targeting studies; Figure a shows the uptake of nanoparticles by vascular endothelial cells in different treatment groups by flow cytometry; Figure b shows the quantitative analysis of the average fluorescence intensity of cells in each group; Figure c shows the uptake of nanoparticles by vascular endothelial cells in different treatment groups by confocal fluorescence microscopy, where cell nuclei are blue and nanoparticles are red, with a scale bar of 20 μm; Figure d shows the quantitative analysis of the fluorescence intensity of nanoparticles in the confocal image.

[0026] Figure 9 This study investigated the in vitro photodynamic effects and cytotoxicity of TD@JP1 NPs. Figure a shows the detection of singlet oxygen generation in endothelial cells of different treatment groups using the SOSG probe; green fluorescence represents SOSG, and blue fluorescence represents the cell nucleus. The scale bar is 20 μm. Figure b shows the quantitative analysis of the average fluorescence intensity of SOSG in endothelial cells of each group. Figure c shows the quantitative results of endothelial cell viability after treatment with different concentrations of nanoparticles. Figure d shows the quantitative analysis of the proportion of apoptotic endothelial cells in different treatment groups. Figure e shows the detection of cell apoptosis by Annexin V-FITC / PI double staining combined with flow cytometry. Figure f shows the expression levels of p-Akt, Akt, p-MAPK, MAPK, p-Src, and Src proteins in endothelial cells of each group detected by Western blot, with Vinculin as an internal control. +L indicates light treatment.

[0027] Figure 10 This study investigates the effects of different nanoparticle treatments on the migration and tubular formation of vascular endothelial cells. Figure a shows the migration of endothelial cells in different treatment groups as detected by the Transwell assay (scale bar: 100 μm); Figure b shows the quantitative analysis of the number of migrating cells; Figure c shows the migration of endothelial cells in each group at 0 h and 24 h as observed by the scratch assay (dashed line represents scratch boundary, scale bar: 200 μm); Figure d shows the quantitative analysis of scratch closure rate; Figure e shows the lumen formation of endothelial cells in different treatment groups as observed by the matrix gel tubular formation assay (scale bar: 100 μm); Figure f shows the quantitative analysis of the number of lumen junctions. +L indicates light treatment.

[0028] Figure 11 This study investigated the effects of different nanoparticle treatments on LPS-induced oxidative stress and inflammatory responses in microglia. Figure a shows the ROS levels in microglia detected by the DCFH-DA probe in each group, with green fluorescence representing DCFH-DA and a scale bar of 20 μm. Figure b shows the quantitative analysis of the average fluorescence intensity of DCFH-DA in each group. Figure c shows the expression of TNF-α in microglia detected by immunofluorescence in each group, with green fluorescence representing TNF-α and blue fluorescence representing the cell nucleus, and a scale bar of 20 μm. Figure d shows the quantitative analysis of the average fluorescence intensity of TNF-α in each group. LPS represents lipopolysaccharide stimulation.

[0029] Figure 12 This study investigated the targeted enrichment of TD@JP1 NPs in the eyes of CNV mice. Figure a shows fluorescence imaging of mouse eyes at different time points after intravenous injection of TD NPs, TD@JP1 NPs, and TD@JP1 NPs after receptor blockade treatment; Figure b shows the quantitative analysis of the change in fluorescence intensity of each group over time; Figure c shows fluorescence imaging of retinal tissue sections, where blue represents cell nuclei, red represents nanoparticles, and the scale bar is 50 μm. INL represents the inner nuclear layer, ONL represents the outer nuclear layer, and RPE represents the retinal pigment epithelium. The blockade group was used to verify the specific targeting ability of TD@JP1 NPs to CNV lesions.

[0030] Figure 13 Fundus fluorescein angiography was used to evaluate treatment in CNV mice under different treatment groups. Groups included PBS, TD@JP1 NPs, T NPs + L, TD NPs + L, TD@JP1 NPs + L, and Verteporfin + L. Green fluorescent areas represent vascular leakage at CNV lesions. The TD@JP1 NPs + L group showed weaker fluorescent leakage on days 7 and 14, suggesting its effective inhibition of CNV formation and reduction of vascular leakage. +L indicates light treatment.

[0031] Figure 14This figure shows the histological changes and inflammatory factor expression in the retina of CNV mice under different treatment groups. Figure a shows the H&E staining results of the retinal tissues of each group, with magnified views of the areas within the dashed boxes in the bottom row. The scale bars are 100 μm and 50 μm, respectively. Figure b shows the expression of TNF-α in the retinal tissue detected by immunofluorescence, with green fluorescence representing TNF-α and blue fluorescence representing cell nuclei. The scale bar is 50 μm. Figure c shows the quantitative analysis of the average fluorescence intensity of TNF-α. Figure d shows the expression of IL-6 in the retinal tissue detected by immunofluorescence, with green fluorescence representing IL-6 and blue fluorescence representing cell nuclei. The scale bar is 50 μm. Figure e shows the quantitative analysis of the average fluorescence intensity of IL-6. +L indicates light treatment.

[0032] Figure 15 To evaluate the safety of different treatments on mouse ocular tissues. Figure a shows the anterior segment appearance of mice in each group; Figure b shows the corneal fluorescein staining results; Figure c shows the anterior segment optical coherence tomography (OCT) image; Figure d shows the fundus fluorescein angiography image; Figure e shows the fundus vascular map, retinal blood flow map, and retinal OCT image; Figure f shows the H&E staining results of ocular tissues, with magnified views of the retina and cornea below (scale bar 100 μm); Figure g shows the quantitative analysis of total retinal thickness; Figure h shows the TUNEL staining results of retinal tissue, where blue represents cell nuclei and green represents TUNEL positive signals (scale bar 100 μm); Figure i shows the quantitative analysis of the average TUNEL fluorescence intensity. +L indicates light treatment, Ver indicates verteporfin, INL indicates the inner nuclear layer, and ONL indicates the outer nuclear layer. Detailed Implementation

[0033] The advantages and features of this application will be described below with reference to specific implementation schemes, but this application is not limited thereto.

[0034] Design and Synthesis of ROS-Responsive Photodynamic Molecule TD

[0035] 1.1 This application designs and synthesizes a multifunctional photosensitizing molecule, TD, which possesses both photodynamic activity and ROS-triggered drug release function. Its molecular construction sequentially includes the construction of a photosensitizing core, the introduction of a functional fragment, and the coupling of a responsive prodrug. First, using benzo[a]selenide diazole, which has strong electron-withdrawing ability, as the parent core, a Suzuki coupling reaction is carried out with 4-(bis(4-methoxyphenyl)amino)phenylboronic acid to introduce a triphenylamine derivative as a strong electron-donating group, constructing a donor-acceptor type conjugated backbone. This structure enhances the intramolecular charge transfer effect, endows TD with long-wavelength response characteristics, and provides a structural basis for its efficient generation of singlet oxygen as a photosensitizer. Subsequently, a functional motif containing 4-hydroxybenzophenone is introduced through a Suzuki coupling reaction. This motif, on the one hand, can prolong the conjugation degree of the molecule, further improving its photophysical properties; on the other hand, it can provide a chemically reactive phenolic hydroxyl site as a reaction site for connecting a ROS-responsive prodrug. In the construction of the ROS-responsive module, the Src kinase inhibitor dasatinib was coupled to a carboxylic acid derivative containing a thioketal linker via an amide condensation reaction to prepare a ROS-cleavable dasatinib prodrug. The thioketal bond exhibits good chemical stability under normal physiological conditions, but it can undergo specific cleavage in the high-concentration ROS environment generated during photodynamic therapy, thereby enabling on-demand release of dasatinib at the lesion site and reducing non-specific drug exposure. Finally, the terminal carboxyl group of the prodrug molecule was coupled to the phenolic hydroxyl group of intermediate T via an esterification reaction to complete the synthesis of the target molecule TD.

[0036] 1.2 Using the hydrophobic multimodal organic molecule TD as a hydrophobic core, a biocompatible amphiphilic biomedical polymer material was coupled with the JP1 peptide, which possesses both angiogenesis targeting and anti-inflammatory activity, to prepare a JP1-modified amphiphilic carrier. This carrier was then co-assembled with the hydrophobic multifunctional molecule TD to prepare TD@JP1 nanoparticles. This design can prolong the in vivo circulation time of the nanosystem, enhance its targeted retention and accumulation in pathological neovascularization areas, reduce non-specific clearance, and regulate local inflammatory responses, thereby achieving precise intervention and synergistic treatment of the CNV lesion microenvironment.

[0037] Beneficial effects achieved: TD@JP1 nanoparticles possess multiple functions, including lesion targeting, photodynamic therapy, ROS-responsive drug release, and anti-inflammatory regulation. The JP1-modified amphiphilic carrier improves the dispersion stability and biocompatibility of the nanoparticles, prolongs their in vivo circulation time, and enhances their recognition, retention, and accumulation on CNV pathological neovascularization endothelial cells. Irradiation induces TD to generate singlet oxygen, which rapidly damages pathological neovascularization and reduces vascular leakage, while simultaneously promoting thioketal bond cleavage, achieving accelerated release of dasatinib at the lesion site. Released dasatinib can continuously inhibit Src-related angiogenesis signals, reduce endothelial cell proliferation, migration, and tubular formation, and reduce off-target toxicity caused by free drug. Furthermore, JP1 and dasatinib can jointly reduce oxidative stress and pro-inflammatory responses in activated microglia, improving the local inflammatory microenvironment of CNV. Therefore, this material can achieve rapid ablation, sustained inhibition, and inflammatory regulation of pathological neovascularization, improving the therapeutic effect of CNV and enhancing overall biocompatibility.

[0038] Terminology Explanation:

[0039] (1) Choroidal Neovascularization (CNV): Choroidal neovascularization refers to an abnormal network of blood vessels that forms beneath the choroid or retina, often accompanied by incomplete vascular structure, blood and fluid leakage, and local inflammatory reactions. CNV is a major pathological basis for neovascular age-related macular degeneration and diabetic retinopathy. Its formation mechanism involves abnormal proliferation of endothelial cells, overexpression of angiogenic factors, activation of immune cells, and pathological vascular remodeling, ultimately leading to damage to the retinal pigment epithelium and decreased central vision.

[0040] (2) Photodynamic Therapy (PDT): PDT is a treatment method that utilizes photosensitizers to generate reactive oxygen species (ROS) under irradiation with light of a specific wavelength to selectively destroy diseased tissue. The photosensitizer is transferred to an excited state under light irradiation and reacts with oxygen molecules to generate ROS, inducing apoptosis of diseased blood vessels or cells, thus achieving precise ablation of local tissue. PDT has been widely used in the treatment of ophthalmic diseases, tumors, and other local lesions; however, its use alone is often limited by angiogenesis and inflammatory responses, and its therapeutic effect is easily affected by the lesion microenvironment.

[0041] (3) Vascular Endothelial Growth Factor (VEGF): VEGF is a glycoprotein secreted by endothelial cells and other cells, primarily regulating angiogenesis, vascular permeability, and endothelial cell migration. VEGF promotes endothelial cell proliferation and lumen formation through the VEGF / VEGFR signaling pathway, and is a core driver of pathological angiogenesis. Abnormally elevated VEGF levels are closely related to CNV and tumor angiogenesis, and therefore are often used as a key target for anti-angiogenic therapy.

[0042] (4) Reactive Oxygen Species (ROS): ROS include highly reactive oxidizing molecules such as singlet oxygen, superoxide anion, hydrogen peroxide, and hydroxyl radicals. In photodynamic therapy, ROS can induce lipid peroxidation, protein oxidation, and DNA damage, thereby inducing occlusion of diseased cells or blood vessels. Although ROS can selectively ablate lesions during treatment, excessive accumulation may also trigger local inflammatory responses. Therefore, the design of treatment platforms must consider both ROS generation activity and anti-inflammatory regulation.

[0043] (5) Anti-inflammatory peptides: Anti-inflammatory peptides are a class of short peptides or functional peptides that reduce local inflammatory responses by inhibiting the expression of inflammatory factors or regulating the activity of immune cells. In the treatment of CNV, anti-inflammatory peptides can inhibit the excessive activation of microglia and macrophages, reduce the release of inflammatory mediators such as TNF-α, IL-1β, and IL-6, and protect the retinal pigment epithelium and surrounding tissues from secondary inflammatory damage, thereby improving the safety and efficacy of treatment. Example

[0044] The preferred embodiments of this application are described in detail below through specific examples, but this application is not limited thereto.

[0045] Unless otherwise specified, the reaction solvents, testing methods, and testing equipment used in the following examples are all conventional reaction solvents, testing methods, and equipment in the art. Example 1: Synthesis of TD

[0046] 1.1 Under argon protection, 4-(bis(4-methoxyphenyl)amino)phenylboronic acid (2.0 g, 5.73 mmol), 4,7-dibromobenzo[c][1,2,5]selenodiazole (1.95 g, 5.73 mmol), tetrakis(triphenylphosphine)palladium (330 mg, 0.286 mmol), and potassium carbonate (2.37 g, 17.18 mmol) were added to a dry reaction flask. A degassed THF / H₂O mixed solvent (v / v 4:1, total volume 62.5 mL) was then added, and the mixture was heated to reflux under argon protection for 18 hours, with the reaction progress monitored by thin-layer chromatography. After the reaction was complete, the reaction solution was cooled to room temperature, diluted with water, and extracted with dichloromethane. The combined organic phases were washed successively with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using n-hexane / dichloromethane (v / v 5:1 to 2:1) as eluent to give a dark red solid 4-(7-bromobenzo[c][1,2,5]selenodiazole-4-yl)- N , N - bis(4-methoxyphenyl)aniline, i.e., compound 3, with a yield of 49.6%. 1 H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.6 Hz, 1H), 7.66 (d, J = 8.7 Hz, 2H), 7.30 (d, J = 7.4 Hz, 1H), 7.19-7.07 (m, 4H), 7.02 (d, J = 8.5 Hz, 2H), 6.90-6.75 (m, 4H), 3.79 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 157.48, 157.43, 155.18, 148.06, 139.32, 134.32, 131.35, 129.02, 127.51, 126.04, 125.94, 118.36, 113.75, 113.39, 54.42.

[0047] 1.2 Under argon protection, (4-bromophenyl)(4-hydroxyphenyl) methyl ketone (3.0 g, 10.83 mmol), bis(pinacol)boronic acid ester (4.14 g, 16.25 mmol), potassium acetate (3.18 g, 32.50 mmol), and [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (441 mg, 0.54 mmol) were added to a dry reaction flask. Anhydrous 1,4-dioxane (60 mL) was added, and the reaction was stirred at 90 °C for 16 h under inert gas protection, with the reaction progress monitored by thin-layer chromatography. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic phases were combined, washed successively with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with hexane / ethyl acetate (v / v 20:1 to 10:1) as eluent to give a white solid (4-hydroxyphenyl)[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)phenyl] ketone, i.e., compound 5, in a yield of 32.5%. 1 H NMR (400MHz, CDCl3) δ 7.91 (d, J = 8.1 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.1 Hz, 2H), 6.90 (d, J = 8.7 Hz, 2H), 5.62 (s, 1H), 1.37 (s, 12H). 13 C NMR (101 MHz, CDCl3) δ196.39, 160.58, 140.45, 134.54, 133.05, 129.75, 115.32, 84.25, 24.88.

[0048] 1.3 Under argon protection, compound 3 (1.50 g, 2.65 mmol, 1.0 equivalence), compound 5 (860 mg, 2.65 mmol), tetrakis(triphenylphosphine)palladium (153 mg, 0.133 mmol), and potassium carbonate (1.10 g, 7.96 mmol) were added to a dry reaction flask. A degassed THF / H₂O mixture (40 mL THF, 10 mL H₂O) was then added, and the mixture was heated under reflux for 12 hours under argon protection, with the reaction progress monitored by thin-layer chromatography. After the reaction was complete, the reaction solution was cooled to room temperature, diluted with water, and extracted with dichloromethane. The combined organic phases were washed successively with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane / methanol (v / v 100:1 to 30:1) as the eluent to give a deep red solid intermediate T in 62.5% yield.1 H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.4 Hz, 2H), 7.92 (d, J = 8.3 Hz, 2H), 7.86 (d, J = 8.7 Hz, 2H), 7.75 (d, J = 8.7 Hz, 2H), 7.68 (d, J = 7.2 Hz, 1H), 7.60 (d, J = 7.2 Hz, 1H), 7.15 (d, J =8.9 Hz, 4H), 7.05 (d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 9.0 Hz, 4H), 3.82 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 195.46, 160.83, 160.69, 159.81, 159.55, 156.21, 149.07, 141.76, 140.51, 137.58, 135.67, 132.97, 132.39, 132.23, 132.16, 132.06, 130 .13, 130.05, 130.01, 129.78, 129.74, 129.42, 129.27, 129.24, 128.99, 128.81, 128.68, 127.14, 119.52, 115.38, 115.33, 114.81, 55.54.

[0049] 1.4 Under argon protection, dasatinib (2.0 g, 4.10 mmol), compound 6 (i.e., propane-2,2-dimethylbis(thio)diacetic acid, 1.03 g, 4.10 mmol), EDCI (i.e., 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 1.18 g, 6.15 mmol), HOBt (831 mg, 6.15 mmol), and NMM (i.e., N-methylmorpholine, 1.24 g, 12.30 mmol) were dissolved in anhydrous water. N,NThe mixture was stirred in dimethylformamide (40 mL) at room temperature for 24 hours. After the reaction was complete, the reaction solution was diluted with water and extracted with dichloromethane. The organic phases were combined, washed successively with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane / methanol (v / v 10:1) as the eluent to give a white solid ROS-responsive dasatinib prodrug, compound 7, in 72.6% yield. 1 H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 8.22 (s, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.30-7.22 (m, 2H), 6.05 (s, 1H), 4.21-4.13 (m, 2H), 3.51 (s, 4H), 2.76 (dt, J = 19.2, 7.1 Hz, 4H), 2.61 (t, J = 6.9 Hz, 5H), 2.51 (d, J = 7.2 Hz, 5H), 2.40 (s, 3H), 2.23 (s, 3H), 1.53 (s, 6H). 13 C NMR (101 MHz, DMSO-d6) δ 173.40, 171.85, 171.83, 165.65, 163.06, 162.84, 160.41, 157.42, 141.30, 139.30, 134.01, 132.92, 129.49, 128.63, 127. 48, 126.18, 119.44, 110.29, 83.12, 62.01, 56.39, 56.33, 52.83, 44.04, 34.57, 34.52, 31.02, 26.05, 25.41, 25.38, 18.78.

[0050] 1.5 Under nitrogen protection, intermediate T (500 mg, 0.732 mmol), compound 7 (529 mg, 0.732 mmol), EDCI (i.e., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) (211 mg, 1.10 mmol), and DMAP (i.e., 4-dimethylaminopyridine, 17.9 mg, 0.146 mmol) were added to a dry reaction flask. Anhydrous DMF (15 mL) was then added, and the reaction was stirred at room temperature for 24 hours under argon protection, with the reaction progress monitored by thin-layer chromatography. After the reaction was complete, the reaction solution was diluted with water and extracted with dichloromethane. The organic phases were combined, washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane / methanol (v / v 100:1 to 20:1) as the eluent to give a deep red solid, target compound TD, in 38.6% yield. 1 H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.0 Hz, 2H), 7.97-7.87 (m, 5H), 7.75 (d, J = 8.3 Hz, 1H), 7.68 (d, J = 7.3 Hz, 1H), 7.59 (d, J = 7.2 Hz, 1H), 7.42 (s, 1H), 7.28 (dd, J = 14.9, 8.2 Hz, 6H), 7.20-7.11 (m, 5H), 7.04 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 8.5 Hz, 3H), 5.77 (s, 1H), 4.27 (t, J = 5.9 Hz, 2H), 3.81 (s, 6H), 3.60 (s, 4H), 3.00 (d, J = 6.7 Hz, 2H), 2.92 (q, J = 7.3Hz, 4H), 2.67 (q, J = 8.3, 7.3 Hz, 4H), 2.57 (s, 4H), 2.49 (s, 3H), 2.34 (s, 3H), 1.64 (s, 6H). High-resolution mass spectrometry (ESI) + ):C 70 H 67 C l N 10 O8S3Se's [M+H] + The theoretical value is 1387.3232, and the measured value is 1387.3225. Example 2: Preparation of TD@JP1 NPs

[0051] T NPs were prepared using a nanoprecipitation method. 1 mg of T and 4 mg of DSPE-PEG were mixed. 2000 (Right now Dissolve 1 mg of TD in 1 mL of tetrahydrofuran, and slowly add the resulting solution to 10 mL of deionized water under continuous vortex conditions. Then stir in a fume hood for 2 hours to allow the tetrahydrofuran to fully evaporate, obtaining T NPs. The obtained nanoparticles were collected and concentrated using a centrifugal ultrafiltration tube with a molecular weight cutoff of 100 kDa. TD NPs were prepared using the same method. In the preparation of TD@JP1 NPs, 1 mg of TD and 1 mg of DSPE-PEG-JP1 (i.e., ) and 3 mg DSPE-PEG 2000 The solution was dissolved in 1 mL of tetrahydrofuran, and the resulting solution was slowly added to 10 mL of deionized water under continuous vortexing. The mixture was then stirred for 2 hours to remove the tetrahydrofuran, yielding TD@JP1 NPs. The obtained nanoparticles were purified using a centrifugal ultrafiltration tube with a molecular weight cutoff of 10 kDa for subsequent experiments. Experimental Example 1: Synthesis and Characterization of TD

[0052] First, according to Figure 1 The synthetic route shown sequentially prepared compound 3, compound 5, photosensitizing intermediate T, ROS-responsive dasatinib prodrug compound 7, and the target molecule TD. Figure 2 As shown, through 1 H NMR analysis of the hydrogen and carbon atom signals of the target product showed results consistent with the expected molecular structure. Figure 3 As shown, TD was further characterized using high-resolution mass spectrometry, and its [M+H]... + The theoretical value was 1387.3232, and the measured value was 1387.3225. The two values ​​are in high agreement, indicating that the target molecule TD, which has both photodynamic activity and ROS-responsive dasatinib release function, was successfully synthesized. Experimental Example 2: Characterization of the optical properties of TD

[0053] First, the photophysical properties of the photosensitive molecule T and the dasatinib-conjugated prodrug TD were characterized. For example... Figure 4 As shown, the maximum absorption peaks of both T and TD are located at approximately 485 nm, and the maximum emission peaks are located at approximately 700 nm, indicating that the coupling of dasatinib did not significantly alter the original optical properties of the photosensitive molecule T.

[0054] The photodynamic properties were further evaluated using three singlet oxygen-specific probes: DPBF, ABDA, and SOSG. Figure 5As shown in Figure a, after 5 minutes of illumination, the reduction rates of DPBF absorption signal by T NPs, TD NPs, and verteporfen were 98%, 91%, and 79%, respectively. Figure 5 As shown in b, the reduction rates of the ABDA absorption signal are 42%, 39%, and 22%, respectively. Figure 5 As shown in c, the SOSG detection results show that the fluorescence signals generated by T NPs and TD NPs are 1.6 times and 1.4 times that of verteporfen, respectively, indicating that TD has good singlet oxygen generation capacity in both organic and aqueous environments. Figure 5 As shown in d, after five consecutive light cycles, the absorption intensity of T NPs and TD NPs changed only slightly, demonstrating excellent photostability. Experimental Example 3: ROS-responsive drug release study of TD

[0055] like Figure 6 As shown, TD basically does not release DAS under the condition of no H2O2 stimulation; after the addition of H2O2, the ROS-responsive TK bond breaks and the amount of DAS released increases significantly, indicating that TD has good ROS responsiveness and drug release capability on demand. Experimental Example 4: Basic Characterization of TD@JP1 NPs

[0056] The hydrophobic prodrug TD and DSPE-PEG were prepared using a nanoprecipitation method. 2000 TD@JP1 NPs were prepared by co-assembling DSPE-PEG-JP1. Figure 7 As shown in figure a, dynamic light scattering results indicate that the hydrated particle size of TD@JP1 NPs is approximately 164.7 nm; transmission electron microscopy reveals that the nanoparticles exhibit a uniform, regular spherical structure. Figure 7 As shown in b, the maximum absorption peak of TD@JP1 NPs is located at approximately 500 nm, and the maximum emission peak is located at approximately 710 nm, indicating that the JP1 modification and nano-assembly process did not significantly affect the optical properties of the photosensitive molecules. Experimental Example 5: In vitro cell-targeting study of TD@JP1 NPs

[0057] like Figure 8 As shown in a and 8b, flow cytometry results indicated that vascular endothelial cells took up approximately 2.1 times more TD@JP1 NPs than untargeted TD NPs. Figure 8As shown in c and 8d, confocal imaging results further revealed that the intracellular fluorescence intensity of the TD@JP1 NPs group was 3.3 times and 3.6 times that of the TD NPs group and the receptor blocking group, respectively. Pretreatment with excessive DSPE-PEG-JP1 to block the integrin receptor significantly reduced cellular uptake of TD@JP1 NPs, indicating that its enhanced endothelial cell uptake mainly depends on the specific recognition between JP1 and integrin αvβ3. Experimental Example 6: In vitro photodynamic effects and cytotoxicity of TD@JP1 NPs

[0058] The singlet oxygen generation capacity of different nanoparticles in vascular endothelial cells was detected using SOSG probes. Figure 9 As shown in a and 9b, TD@JP1 NPs can efficiently generate singlet oxygen in vascular endothelial cells under light conditions, and their SOSG fluorescence intensity is significantly higher than that of the T NPs and TD NPs groups. Figure 9 As shown in c, 9d, and 9e, TD@JP1 NPs exhibited low basal cytotoxicity under light-free conditions, but showed significant concentration-dependent cytotoxicity after light exposure, increasing the proportion of non-viable and apoptotic cells to 43.7%, significantly higher than the T NPs and TD NPs light-exposed groups. Figure 9 As shown in f, Western blot results showed that both TD NPs and TD@JP1 NPs reduced the phosphorylation levels of Src, AKT, and MAPK after light irradiation, with TD@JP1 NPs showing a more significant inhibitory effect. This indicates that JP1-mediated cell targeting and light-triggered dasatinib release can synergistically enhance the inhibition of pro-angiogenic signals in Src / AKT / MAPK. Experimental Example 7: Evaluation of the effects of different nanoparticles on vascular endothelial cell migration and tube formation.

[0059] The in vitro anti-angiogenic ability of different nanoparticles was evaluated using Transwell migration assays, cell scratch assays, and Matrigel tube formation assays. Figure 10 As shown in a and 10b, compared with the PBS group, TD@JP1 NPs combined with light treatment reduced the number of migrating cells by approximately 8.3-fold, and by approximately 3.2-fold and 1.8-fold, respectively, compared with the T NPs and TD NPs light-treated groups. Figure 10 As shown in c and 10d, the scratch closure rate of the TD@JP1 NPs combined illumination group was only 2.6%, significantly lower than the 12.6% of the TD NPs illumination group and the 16.8% of the TNPs illumination group. Figure 10As shown in e and 10f, the PBS group formed a complete and dense capillary-like network, while the luminal structure of the TD@JP1 NPs combined with light irradiation group was significantly disrupted, with the number of connection points decreasing from 148 in the PBS group to approximately 30. These results indicate that TD@JP1 NPs, after photoactivation, can significantly inhibit the migration and tube-forming ability of vascular endothelial cells. Experiment Example 8: Study on the effects of different nanoparticles on LPS-induced oxidative stress and inflammatory response in microglia

[0060] A BV2 microglial inflammation model was established using LPS, and intracellular ROS levels were detected using the DCFH-DA probe. Figure 11 As shown in a and 11b, LPS stimulation significantly increased intracellular ROS in BV2 cells. TD NPs treatment partially reduced ROS accumulation, while TD@JP1 NPs showed a more pronounced inhibitory effect, reducing ROS signal to approximately one-sixth of that in the LPS / PBS group, approaching the level of unstimulated cells. Figure 11 As shown in c and 11d, TD@JP1 NPs significantly reduced TNF-α expression, and their anti-inflammatory effect was superior to that of unmodified JP1 TD NPs. These results indicate that JP1-mediated oxidative stress regulation and ROS-responsive dasatinib release can synergistically inhibit microglial inflammatory responses. Experimental Example 9: Targeted enrichment study of TD@JP1 NPs in the eyes of CNV mice.

[0061] A laser-induced CNV mouse model was established, and its ocular targeting enrichment ability was evaluated by intravenous injection of TD NPs, TD@JP1 NPs, and TD@JP1 NPs treated with receptor blockade. Figure 12 As shown in a and 12b, TD@JP1 NPs exhibited stronger and more persistent fluorescence signals in the CNV lesion area. Sixty minutes after injection, the ocular fluorescence intensity of the TD@JP1 NPs group was approximately 1.7 times that of the TDNPs group, while the fluorescence signal was significantly reduced after JP1 pre-blocking. Figure 12 As shown in c and 12d, the fluorescence intensity of the TD@JP1 NPs group was 2.1 times and 2.3 times that of the TD NPs group and the blocking group, respectively. The nanoparticles were mainly distributed in the RPE and choroid complex region. The results indicate that JP1 modification can enhance the targeted enrichment and retention of TD@JP1 NPs in CNV lesions through integrin-mediated recognition. Experimental Example 10: Evaluation of the therapeutic effect of TD@JP1 NPs on CNV using fundus fluorescein angiography

[0062] Fundus fluorescein angiography was used to observe vascular leakage in CNV mice after treatment in different treatment groups. Figure 13As shown, compared with the PBS group, fluorescein leakage was reduced in all phototherapy groups. The therapeutic effect of T NPs combined with phototherapy was similar to that of verteporfen combined with phototherapy. TD NPs and TD@JP1 NPs combined with phototherapy showed more significant CNV inhibition, indicating that dasatinib conjugation and JP1 targeted modification can further improve the photodynamic therapy effect. Experimental Example 11: Histological Changes in the Retinal Tissue and Expression of Inflammatory Factors in CNV Mice under Different Treatment Groups

[0063] The morphology of the retina and choroid of CNV mice in different treatment groups was observed using H&E staining. Figure 14 As shown in Figure a, obvious raised CNV lesions, pigment aggregation, and fibrovascular tissue proliferation were observed in the PBS group and the non-phototherapy group. The pathological structures of all phototherapy groups showed varying degrees of improvement, with the TD@JP1 NPs combined with phototherapy group showing the most significant reduction in CNV tissue proliferation and lesion thickness. Figure 14 As shown in b, 14c, 14d, and 14e, the expression of inflammatory factors such as TNF-α and IL-6 was significantly increased in CNV lesions. Different nanoparticles combined with light irradiation all reduced the levels of inflammatory factors. Among them, the TD@JP1 NPs combined with light irradiation group showed the lowest TNF-α and IL-6 signals, indicating that this system can not only inhibit pathological angiogenesis but also effectively alleviate the local inflammatory microenvironment of CNV. Experimental Example 12: Evaluation of the safety of different treatments on mouse ocular tissues

[0064] The ocular safety of different treatments was comprehensively evaluated using methods such as anterior segment imaging, corneal fluorescein staining, anterior segment optical coherence tomography, fundus fluorescein angiography, fundus vascular imaging, retinal blood flow imaging, and retinal OCT. For example... Figure 15 As shown in Figure a, slit-lamp examination revealed no obvious abnormalities in the cornea, lens, and retina of the mice in each treatment group. Figure 15 As shown in b, sodium fluorescein staining results revealed a mild fluorescent signal on the ocular surface of the light-exposed group, which may be attributed to the transient distribution of the intravenously injected photosensitizer in ocular surface tissues such as the conjunctiva and limbus. The non-specific fluorescent signal on the ocular surface of the TD@JP1 NPs-treated group was significantly weaker, suggesting that the JP1-mediated targeting effect helps reduce non-specific exposure of the photosensitizer to the ocular surface, thereby reducing the risk of potential local irritation and adverse reactions. Figure 15 As shown in Figure c, anterior segment optical coherence tomography further confirmed that photodynamic irradiation did not cause detectable structural damage to anterior segment tissues such as the cornea, conjunctiva, and ciliary body. Figure 15 As shown in d and 15e, fundus photography, fundus angiography, retinal blood flow imaging, and OCT analysis all showed that the retinal vascular structure was intact and no obvious abnormalities were observed. Figure 15As shown in f and 15g, the corneal and retinal tissue structures of each group were basically normal, and there was no significant difference in the total retinal thickness. Figure 15 As shown in h and 15i, almost no obvious apoptosis signal was observed in the TD@JP1 NPs combined with light irradiation group, while a certain degree of apoptosis was observed in the free DAS group. These results indicate that constructing DAS as a ROS-responsive prodrug can effectively reduce its non-specific exposure and toxicity to normal eye tissues, further validating the effectiveness of prodrug design in improving ocular biosafety. This specification is presented in a progressive manner, and similar or identical parts between the various embodiments can be referred to interchangeably.

[0065] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A photosensitive molecule, characterized in that, It comprises a triphenylamine-benzoselenide diazole structural unit, a 4-oxybenzophenone structural unit, a dialkyl carbonyl structural unit containing a thioketal linker arm, and a dasatinib structural unit with the terminal hydroxyl hydrogen atom removed, wherein the alkyl group has 1-20 carbon atoms.

2. The photosensitive molecule according to claim 1, characterized in that, The alkyl group has 1-10 carbon atoms, preferably 2-6.

3. The photosensitive molecule according to claim 1, characterized in that, The structure of the photosensitive molecule is as follows: 。 4. A method for preparing a photosensitive molecule according to any one of claims 1 to 3, characterized in that, The method includes the following steps: Under inert gas protection, 4,4-dimethoxy-4-boronic acid triphenylamine, 4,7-dibromobenzo[c][1,2,5]selenodiazole, a first catalyst, and a first base were added to a first reactor, followed by the addition of a first reaction solvent. The mixture was heated under reflux to obtain the first reaction product. Under inert gas protection, (4-bromophenyl)(4-hydroxyphenyl) methyl ketone, dipinacol boronic acid ester, second catalyst, and second base are added to the second reactor, followed by the addition of the second reaction solvent. The reaction is carried out at a certain temperature to obtain the second reaction product. Under inert gas protection, the first reaction product, the second reaction product, the third catalyst, and the third base are added to the third reactor, and then the third reaction solvent is added. The mixture is heated under reflux to obtain the third reaction product. Under inert gas protection, dasatinib, propane-2,2-dimethylbis(thio)diacetic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-methylmorpholine were dissolved in the fourth reaction solvent and reacted with stirring at room temperature to obtain the fourth reaction product. Under inert gas protection, the third reaction product, the fourth reaction product, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 4-dimethylaminopyridine are added to the fifth reaction solvent, and the reaction is stirred at room temperature to obtain the photosensitive molecule.

5. The method according to claim 4, characterized in that, The inert gases include nitrogen, helium, neon, and argon; the first catalyst and the third catalyst include tetratetraphenylphosphine palladium, 1,1'-bis(diphenylphosphine)ferrocene palladium(II) chloride, and a 1,1'-bis(diphenylphosphine)ferrocene palladium(II) chloride dichloromethane complex; the first base and the third base are alkali metal carbonates, preferably potassium carbonate and sodium carbonate; the first reaction solvent and the third reaction solvent are mixed solvents of inorganic and organic solvents, wherein the inorganic solvent includes water, and the organic solvent includes tetrahydrofuran, 1,4-dioxane, and... N,N -Dimethylformamide, wherein the volume ratio of the organic solvent to the inorganic solvent is 2:1 to 6:1, preferably 4:1; the second catalyst is a tetratetraphenylphosphine palladium, 1,1'-bis(diphenylphosphine)ferrocene palladium(II) chloride, and a 1,1'-bis(diphenylphosphine)ferrocene palladium(II) chloride dichloromethane complex; the second base includes alkali metal acetate, preferably potassium acetate and sodium acetate; the second reaction solvent includes 1,4-dioxane, N,N -Dimethylformamide, tetrahydrofuran; the first temperature is 60-120 degrees Celsius, preferably 90 degrees Celsius; the fourth reaction solvent and the fifth reaction solvent are organic solvents, including tetrahydrofuran, 1,4-dioxane, N,N -Dimethylformamide.

6. A nanoparticle, characterized in that, The nanoparticles are co-assembled, which are formed by co-assembling a JP1-modified amphiphilic carrier with a photosensitive molecule according to any one of claims 1 to 3.

7. The nanoparticles according to claim 6, characterized in that, The JP1-modified amphiphilic carrier is formed by coupling an amphiphilic biomedical polymer material with good biocompatibility with a JP1 peptide that has both angiogenesis targeting and anti-inflammatory activity.

8. The nanoparticles according to claim 6, characterized in that, The amphiphilic biomedical polymer material with good biocompatibility, polyethylene glycol-modified phospholipid material, is preferably DSPE-PEG, more preferably DSPE-PEG2000. The JP1 peptide, which has both angiogenesis targeting and anti-inflammatory activity, is derived from a seven-amino acid fragment optimized from the JWA protein.

9. The nanoparticles according to claim 6, characterized in that, The nanoparticles possess multiple functions, including lesion targeting, photodynamic therapy, ROS-responsive drug release, and anti-inflammatory regulation.

10. A method for preparing nanoparticles according to any one of claims 6 to 9, characterized in that, The method includes the following steps: applying the photosensitive molecule according to any one of claims 1 to 3, DSPE-PEG-JP1 (i.e., DSPE-PEG2000-Mal-CFPGSDRFGGGRGD), and DSPE-PEG... 2000 Right now The nanoparticles are dissolved in the sixth reaction solvent and the resulting solution is slowly added to deionized water under continuous vortex conditions; then stirred to remove the sixth reaction solvent, thereby obtaining the nanoparticles; the sixth reaction solvent is an organic solvent, including tetrahydrofuran, dimethyl sulfoxide, and toluene.

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