Synergistic photodynamic-photothermal tumor therapy realized by near-infrared ii region aggregation-induced emission nanoparticles

Abstract

The application discloses a kind of near-infrared two-area aggregation-induced emission nanoparticles to realize synergistic photodynamic-photothermal tumor treatment, belong to using aggregation-induced emission material for cancer treatment field.The preparation method of the photosensitive compound of near-infrared two-area aggregation-induced emission of the present application includes the following steps: compound 1, compound 2, tetra-triphenylphosphine palladium, potassium carbonate are mixed in the mixed solution of tetrahydrofuran and water, backflow reaction, obtain compound 3;Compound 3 and R2 are mixed in acetic anhydride, reaction, obtain the photosensitive compound of the near-infrared two-area aggregation-induced emission.The present application successfully prepares a kind of multifunctional photosensitizer by molecular design, which integrates NIR-II excitation, efficient I-type PDT, super high efficiency PTT and AIE characteristics, provides a kind of new technical scheme for solving the bottleneck of hypoxia in tumor treatment and realizing efficient synergistic treatment.

Description

Technical Field

[0001] This invention relates to the use of aggregation-induced emission materials in the field of cancer treatment, and in particular to synergistic photodynamic-photothermal tumor therapy achieved by near-infrared II aggregation-induced emission nanoparticles. Background Technology

[0002] Organic reagents with photosensitizing properties have been widely used in many cutting-edge fields such as tumor therapy, antibacterial agents, and photocatalysis. Among them, hematoporphyrin derivatives (HpD), porphyrins, and phthalocyanine compounds have been widely used as organic photosensitizers because they can generate reactive oxygen species (ROS) under light conditions. Taking hematoporphyrin derivatives as an example, as a representative of the first generation of photosensitizers, they showed a certain inhibitory effect on superficial tumors such as breast cancer metastases in the skin in early clinical studies, establishing the position of photodynamic therapy in tumor treatment.

[0003] However, with in-depth research and increasing clinical demands, these traditional photosensitizers have gradually revealed several key technical bottlenecks. First, their maximum absorption wavelengths are mostly in the ultraviolet or visible light region, resulting in weak tissue penetration and significant light energy attenuation when treating deep solid tumors, thus limiting the effective treatment depth. Second, most commercially available photosensitizers follow a type II photodynamic mechanism, primarily generating singlet oxygen through energy transfer to the ground state oxygen (…). 1 O2), whose reactive oxygen species (ROS) yield is highly dependent on local oxygen concentration, but in the hypoxic microenvironment common in solid tumors, the efficiency of this mechanism is greatly reduced, resulting in a significant weakening of the therapeutic effect. In addition, traditional photosensitizers generally exhibit aggregation-induced quenching (ACQ) effect at high concentrations or in aggregated states, which not only causes self-quenching of fluorescence emission but also severely weakens their ROS generation capacity, greatly limiting the dosage and tumor enrichment effect, and restricting their potential for practical application in clinical practice.

[0004] Therefore, there is an urgent need to design a photosensitizer with a higher excitation wavelength, type I photodynamic properties, and aggregation-induced emission properties to solve the problems of low penetration depth, weak ability to generate reactive oxygen species under hypoxic conditions, and aggregation-induced quenching of traditional photosensitizers. Summary of the Invention

[0005] The purpose of this invention is to provide a synergistic photodynamic-photothermal tumor therapy achieved through near-infrared II aggregation-induced emission nanoparticles, thereby addressing the aforementioned problems in the prior art. Through molecular design, this invention successfully prepares a multifunctional photosensitizer integrating NIR-II excitation, highly efficient type I photothermal photothermal (PDT), ultra-high efficiency photothermal (PTT), and active oxygen emission (AIE) properties, providing a novel technical solution for overcoming the hypoxia bottleneck in tumor treatment and achieving highly efficient synergistic therapy.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] One of the technical solutions of this invention is to provide a photosensitive compound with near-infrared II aggregation-induced emission, the general structural formula of which is as follows:

[0008] ;

[0009] Where R1 is , , , , , , or ;

[0010] R2 is , , , , , or .

[0011] Preferably, the photosensitive compound for near-infrared II aggregation-induced emission contains a material with one of the following structural formulas:

[0012] .

[0013] The photosensitive compounds defined in this invention are aggregation-induced emission molecules (AIEgens) with a donor-acceptor (DA) structure, possessing a strong electron donor unit and a strong electron acceptor unit. The DA structure design of this invention can redshift the absorption and emission spectra of the molecules to the near-infrared window (especially 808 nm laser excitation), achieving deeper tissue penetration and significantly promoting intersystem crossing (ISC) processes, thereby increasing singlet oxygen (…). 1 The photosensitive compound amplifies its photodynamic therapeutic effects by increasing the quantum yield of O2 or other reactive oxygen species (ROS). It possesses AIE properties, exhibiting enhanced fluorescence and ROS generation capabilities in the aggregated state or after being fabricated into nanoparticles, overcoming the concentration quenching problem.

[0014] The second technical solution of the present invention provides a method for preparing the above-mentioned near-infrared II region aggregation-induced emission photosensitive compound, comprising the following steps:

[0015] (1) Compound 1, compound 2, tetratriphenylphosphine palladium, and potassium carbonate were mixed in a mixed solution of tetrahydrofuran and water and refluxed to obtain compound 3;

[0016] (2) Compound 3 and compound 4 were mixed in acetic anhydride and reacted to obtain the photosensitive compound with near-infrared II aggregation-induced emission;

[0017] Among them, compound 1 is Compound 2 is Compound 3 is Compound 4 is , , , , , or .

[0018] Preferably, the reaction is carried out at a temperature of 75°C for 8 hours in an oxygen-free atmosphere.

[0019] Preferably, the preparation method of compound 1 includes the following steps:

[0020] Compound a ( ), compound b ( Tris(dibenzylacetone)palladium (Pd2(Dba)3), sodium tert-butoxide (OtBuNa), and 1,1'-bis(diphenylphosphine)ferrocene were dissolved in ultra-dry toluene and reacted under nitrogen reflux for 24 h. The mixture was then extracted with dichloromethane, washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography, dichloromethane, and petroleum ether to obtain compound c (DTP).

[0021] Compound c was dissolved in tetrahydrofuran, and diisopropylaminolithium was added dropwise at -78°C for 1 h. Anhydrous N,N-dimethylformamide was then added, and the reaction mixture was kept at -78°C for 1 h. The mixture was then heated to room temperature and kept for 2 h. After quenching with water, the mixture was extracted with dichloromethane, washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography, dichloromethane, and petroleum ether to give compound d (DTP-CHO).

[0022] Compound d was dissolved in dichloromethane, N-bromosuccinimide was added, and the mixture was stirred for 4 h. The mixture was then extracted with dichloromethane, washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography, dichloromethane, and petroleum ether to obtain compound 1 (DTP-CHO-Br).

[0023] More preferably, the preparation method includes the following steps:

[0024]

[0025] The third technical solution of the present invention provides a near-infrared II aggregation-induced emission nanoparticle, which contains the aforementioned near-infrared II aggregation-induced emission photosensitive compound.

[0026] The fourth technical solution of the present invention provides a method for preparing the above-mentioned near-infrared II aggregation-induced emission nanoparticles, wherein the photosensitive compound of near-infrared II aggregation-induced emission is prepared into nanoparticles (NPs) by nanoprecipitation or emulsification.

[0027] More preferably, the preparation method includes the following steps:

[0028] The photosensitive compound and stabilizer in the near-infrared II region aggregation-induced emission region were mixed in an organic solvent to obtain an organic phase;

[0029] The organic phase is injected into the aqueous phase under shear force to obtain a mixed solution. The mixed solution is then stirred overnight in a fume hood to completely remove the organic solvent and obtain a suspension.

[0030] The suspension was filtered through a filter membrane to obtain a uniformly dispersed aqueous solution of near-infrared II aggregation-induced emission nanoparticles (DTPTMI NPs).

[0031] More preferably, the stabilizer is DSPE-PEG2000; the mass ratio of the photosensitive compound and the stabilizer in the near-infrared II region aggregation-induced emission region is 1-5:1-10; and the organic solvent is tetrahydrofuran or dimethyl sulfoxide.

[0032] More preferably, the shear force is applied by magnetic stirring or ultrasound; the rotation speed of the magnetic stirring is 800-1500 rpm; and the pore size of the filter membrane is 0.22 μm or 0.45 μm.

[0033] Fifth technical solution of the present invention: to provide the application of the above-mentioned near-infrared II aggregation-induced emission photosensitive compound or the above-mentioned near-infrared II aggregation-induced emission nanoparticles in the preparation of photosensitizers for tumor phototherapy.

[0034] Preferably, the application is in the preparation of photosensitizers for phototherapy of hypoxic solid tumors.

[0035] Preferably, the light source for the photosensitizer during application is near-infrared light.

[0036] Preferably, the method of using the photosensitive compound or nanoparticles includes the following steps: administering a therapeutically effective amount of the photosensitive compound or nanoparticles to the subject via intravenous injection; after a certain period of time (6-24h) for the drug to accumulate at the tumor site, irradiating the tumor site with an 808 nm near-infrared laser until the irradiation is sufficient to simultaneously excite photodynamic and photothermal effects, thereby achieving synergistic ablation of the tumor.

[0037] The technical principle of this invention is as follows:

[0038] Photodynamic therapy (PDT) performance: The photosensitizer of this invention can efficiently generate reactive oxygen species (ROS) under near-infrared light irradiation (preferably 808 nm laser). The generated ROS are superoxide anions (O2• — Primarily based on oxygen concentration in the environment, it follows a type I photodynamic mechanism. This mechanism is independent of the oxygen concentration in the environment, thus maintaining a highly efficient killing effect even in the hypoxic microenvironment of tumors.

[0039] Photothermal therapy (PTT) performance: Nanoparticles made from compounds (DTPTMM, DTPTMI) of the specific structure of this invention exhibit excellent photothermal effects under 808 nm laser irradiation. Their photothermal conversion efficiency (PCE) is extremely high, reaching 87.4%, which is higher than most known organic photothermal agents.

[0040] Synergistic treatment mechanism: The product of this invention possesses both type I PDT and PTT functions, enabling synergistic treatment. The local hyperthermia generated by PTT can promote blood flow at the tumor site, improve the hypoxic environment, and further accelerate the generation efficiency of ROS; at the same time, the chemical killing of PDT and the thermal ablation of PTT work together to target tumor cells, achieving a therapeutic effect of "1+1>2".

[0041] The beneficial technical effects of the present invention are as follows:

[0042] 1. Near-infrared excitation and deep tissue therapy capabilities: Through the donor-receptor (DA) structure design defined in this invention, the excitation wavelength of the photosensitizer can be red-shifted to the near-infrared (NIR) window of 808 nm. This wavelength is located in the first transparency window of biological tissue, possessing deeper tissue penetration capability and lower tissue background fluorescence interference, laying the foundation for the treatment of deep tumors.

[0043] 2. High reactive oxygen species yield and enhanced photodynamic therapy: The DA strong interaction unit of this invention not only modulates the spectrum but also effectively promotes the intersystem crossing (ISC) process of molecules, significantly amplifying its inherent photodynamic efficiency. This means that under the same illumination conditions, the photosensitizer of this invention can generate a greater amount of reactive oxygen species (ROS), thereby exhibiting superior tumor cell killing ability.

[0044] 3. Unique Type I mechanism and excellent hypoxia tolerance: The photosensitizers (DTPTMM, DTPTMI) of this invention mainly produce superoxide anions (O2•) under 808nm laser irradiation. — This is a type I photodynamic mechanism of reactive oxygen species. The type I mechanism does not depend on a hyperoxia environment, so it can still maintain a strong cytotoxic effect in the hypoxic microenvironment commonly found inside solid tumors. This overcomes the problem of the sharp decrease in efficacy of traditional type II photosensitizers under hypoxic conditions, and achieves highly efficient "hypoxic-resistant tumor therapy".

[0045] 4. Superior Photothermal Conversion Efficiency and Synergistic Therapeutic Function: The product of this invention exhibits outstanding photothermal therapy (PTT) performance, with a photothermal conversion efficiency (PCE) as high as 87.4%, which is superior to most reported organic photothermal reagents. The product of this invention simultaneously possesses both type I photodynamic therapy (PDT) and photothermal (PTT) functions, providing the possibility for synergistic therapy.

[0046] 5. Synergistic Antitumor Effect: The product of this invention can simultaneously induce synergistic therapeutic effects of PDT and PTT under 808 nm single laser irradiation. The local hyperthermic effect generated by PTT can not only directly ablate the tumor, but also promote blood perfusion at the tumor site and relieve hypoxia, thereby further enhancing the efficacy of type I PDT. The two complement each other, ultimately demonstrating a superior tumor suppression effect far exceeding that of single therapy in the 4T1 tumor-bearing mouse model.

[0047] 6. AIE Properties and High Stability: The photosensitive compound of this invention possesses aggregation-induced emission (AIE) properties. Compared to its fluorescence effect in the dispersed state, the luminescence of this photosensitive compound is enhanced in the aggregated state or after being formed into nanoparticles. This property avoids the concentration quenching (ACQ) effect of traditional fluorophores at high concentrations, ensuring that it maintains high optical activity and ROS generation capacity even after accumulation at the tumor site, thereby improving the signal-to-noise ratio and efficacy of diagnosis and treatment.

[0048] In summary, this invention has successfully prepared a multifunctional photosensitizer integrating NIR-II excitation, high-efficiency type I PDT, ultra-high-efficiency PTT, and AIE characteristics through molecular design, providing a novel technical solution for solving the hypoxia bottleneck in tumor treatment and achieving efficient synergistic therapy. Attached Figure Description

[0049] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0050] Figure 1 The graphs show the absorption and emission curves of DTPTMI and DTPTMM. The left graph shows the absorption curve, and the right graph shows the emission curve.

[0051] Figure 2 Comparison of photodynamic effect curves for DTPTMI and DTPTMM.

[0052] Figure 3 Statistical data on particle size and microstructure of DTPTMI NPs.

[0053] Figure 4 Comparison of photodynamic effect curves for DTPTMI NPs and DTPTMM NPs.

[0054] Figure 5 The photothermal conversion efficiency curves of DTPTMI NPs are shown.

[0055] Figure 6 Photothermal imaging of mice after DTPTMI NPs were injected into them and the location was irradiated with laser for different durations.

[0056] Figure 7 The curve showing the change in tumor volume after DTPTMI NPs were injected into mice.

[0057] Figure 8 Immunofluorescence sections of tumor tissue. Detailed Implementation

[0058] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0059] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0060] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. It should be noted that any aspects of this invention not described in detail are conventional practices in the art and are not the focus of this invention.

[0061] The terms “comprising,” “including,” “having,” “containing,” etc., used in this invention are all open-ended terms, meaning that they include but are not limited to.

[0062] Unless otherwise specified, "room temperature" in this invention refers to 10-30°C.

[0063] Unless otherwise specified, "overnight" in this invention refers to 12 hours.

[0064] All raw materials used in the following embodiments and comparative examples of the present invention are commercially available products.

[0065] Example 1

[0066] A near-infrared II aggregation-induced emission photosensitizer (DTPTMI) is prepared as follows:

[0067] Compound a ( 5 mmol), compound b ( 0.05 mmol of tridibenzylacetone dipalladium (Pd2(Dba)3, 0.05 mmol), sodium tert-butoxide (OtBuNa, 20 mmol), and 1,1'-bis(diphenylphosphine)ferrocene (DPPF, 0.1 mmol) were dissolved in ultra-dry toluene (25 mL) and reacted under nitrogen reflux for 24 h. The mixture was then extracted with dichloromethane, washed with brine, dried with anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography, dichloromethane, and petroleum ether to give compound c (yield 90%).

[0068] 2 mmol of compound c was dissolved in 20 mL of anhydrous tetrahydrofuran (THF). Diisopropylaminolithium (LDA, 2.2 mmol) was added dropwise at -78 °C and maintained for 1 h. Then, anhydrous N,N-dimethylformamide (DMF, 2.2 mmol) was added, and the reaction mixture was maintained at -78 °C for 1 h, followed by warming to room temperature and maintaining for 2 h. After quenching with water, the mixture was extracted with dichloromethane, washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the crude product was purified by silica gel column chromatography followed by dichloromethane and petroleum ether to give compound d (70% yield).

[0069] 2 mmol of compound d was dissolved in dichloromethane (DCM, 10 mL), and N-bromosuccinimide (NBS, 2.2 mmol) was added. The mixture was stirred at room temperature for 4 h. The mixture was then extracted with dichloromethane, washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the crude product was purified by silica gel column chromatography followed by dichloromethane and petroleum ether to give compound e (78% yield).

[0070] 1 mmol of compound e and compound f ( 1.2 mmol of tetraphenylphosphine palladium (Pd(PPh3)4, 0.03 mmol) and potassium carbonate (K2CO3, 2 mmol) were dissolved in a mixed solution of tetrahydrofuran (THF, 10 mL) and water (2 mL). The mixture was refluxed under nitrogen overnight, then extracted with dichloromethane, washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the crude product was purified by silica gel column chromatography followed by dichloromethane and petroleum ether to give compound g (90% yield).

[0071] 0.1 mmol of compound g and compound h ( 0.095 mmol) was dissolved in acetic anhydride (5 mL), and the reaction was carried out under nitrogen protection at 75 °C for 8 h. The reaction was quenched with water, and the crude product was obtained by filtration. The crude product was washed with methanol, EA and n-hexane to give compound DTPTMI (yield 48.2%).

[0072] 1H NMR (400 MHz, Chloroform-d) δ 8.77 (s, 1H), 8.53 (dd, J = 5.9, 3.1Hz, 2H), 7.69 (dd, J = 5.9, 3.1 Hz, 2H), 7.61 (t, J = 7.6 Hz, 2H), 7.57 –7.51 (m, 3H), 7.46 (dd, J = 13.4, 7.9 Hz, 3H), 7.14 (s, 1H), 7.10 (d, J = 8.9Hz, 4H), 6.90 (s, 1H), 6.87 (d, J = 9.0 Hz, 5H), 3.81 (s, 6H). 13C NMR (101MHz, Chloroform-d) δ 160.40, 156.87, 155.19, 153.66, 150.33, 139.76, 138.01, 137.52, 136.53, 133.66, 132.08, 130.33, 127.92, 127.31, 126.93, 125.19, 124.98, 123.44, 122.51, 119.22, 116.52, 115.03, 114.51, 114.36, 105.38, 69.87, 55.51.

[0073] Example 2

[0074] A near-infrared II aggregation-induced emission photosensitizer (DTPTMM) is prepared as follows:

[0075] Take compound g (0.1 mmol) obtained in Example 1 and mix it with compound i ( The compound DTPTMM (0.2 mmol) was dissolved together with acetic anhydride (5 mL) under nitrogen protection and reacted at 75 °C for 8 h. The reaction was quenched with water, filtered to obtain the crude product, which was then dissolved in dichloromethane and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the crude product was purified by silica gel column chromatography, followed by dichloromethane and petroleum ether to give the compound DTPTMM (yield 65.0%).

[0076] 1H NMR (500 MHz, CDCl3) δ 1H NMR (500 MHz, DMSO-d6) δ 8.49 (s, 1H),8.01 (s, 1H), 7.72 (d, J = 7.0 Hz, 2H), 7.65 (t, J = 7.6 Hz, 2H), 7.60 (d, J= 7.7 Hz, 2H), 7.56 (s, 1H), 7.49 (t, J = 6.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 4H), 6.94 (d, J = 8.7 Hz, 4H), 6.76 (d, J = 8.2 Hz, 2H), 3.75 (s, 6H). 13CNMR (101 MHz, DMSO-d6) δ 156.21, 152.71, 150.60, 150.01, 148.99, 142.70,139.35, 137.69, 132.71, 130.27, 128.29, 127.28, 127.19, 126.66, 125.18,123.05, 118.52, 115.73, 115.07, 114.85, 106.40, 68.76, 55.27.

[0077] The synthetic routes for DTPTMI and DTPTMM in Examples 1 and 2 are as follows:

[0078]

[0079]

[0080] Example 3

[0081] A method for preparing near-infrared II aggregation-induced emission nanoparticles (DTPTMI NPs) includes the following steps:

[0082] 1 mg of DTPTMI, the compound prepared in Example 1, and 1 mg of DSPE-PEG2000 were dissolved in anhydrous tetrahydrofuran to obtain an organic phase. This organic phase was then rapidly added to 10 mL of ultrapure water and ultrasonically dispersed until the solution became clear. The remaining tetrahydrofuran was evaporated, and the solution was centrifuged through an ultrafiltration tube to obtain a DTPTMI NPs dispersion with a concentration of 1 mg / mL.

[0083] Example 4

[0084] A method for preparing near-infrared II aggregation-induced emission nanoparticles (DTPTMM NPs) includes the following steps:

[0085] 1 mg of compound DTPTMM prepared in Example 2 and 1 mg of DSPE-PEG2000 were dissolved in anhydrous tetrahydrofuran to obtain an organic phase, which was then rapidly added to 10 mL of ultrapure water and ultrasonically dispersed until the solution became clear. The remaining tetrahydrofuran was evaporated, and the solution was centrifuged through an ultrafiltration tube to obtain a DTPTMM NPs dispersion with a concentration of 1 mg / mL.

[0086] Effect verification

[0087] Figure 1 The graphs show the absorption and emission curves of DTPTMI and DTPTMM. The left graph shows the absorption curve, and the right graph shows the emission curve.

[0088] Figure 1 The excitation wavelength is 808 nm.

[0089] Figure 2 Comparison of photodynamic effect curves for DTPTMI and DTPTMM.

[0090] Figure 2 In this diagram, Ce6 represents a commercially available photosensitizer (purchased from Shanghai Maclean Biochemical Technology Co., Ltd.), and DCFH represents dichlorodihydrofluorescein, a reactive oxygen species detection probe; test conditions: 808 nm, 500 mW / cm². 2 .

[0091] Figure 3 Statistical data on particle size and microstructure of DTPTMI NPs.

[0092] Figure 4 Comparison of photodynamic effect curves for DTPTMI NPs and DTPTMM NPs.

[0093] Figure 4 In the text, DHR123 represents dihydrorhodamine 123, and Blank is the fluorescence background of rhodamine itself.

[0094] Figure 5 The photothermal conversion efficiency curves of DTPTMI NPs are shown.

[0095] The formula for calculating photothermal efficiency is:

[0096] Animal experiments: 5 × 10 6 Four T1 cells were suspended in 100 μL of DMEM and subcutaneously injected into the axilla of BALB / c mice. When the primary tumor reached approximately 125 mm... 3Mice were randomly divided into 4 groups (n=6 per group) and treated as follows: (1) saline; (2) saline + light; (3) DTPTMI NPs; (4) DTPTMI NPs + light. Twelve hours after injection, mice were treated with an 808nm laser (0.3 W / cm²). 2 The light-treated group received light irradiation for 10 minutes, while the dark-treated group received no treatment. The entire treatment period lasted 14 days. During this period, the mice were weighed, and the tumor volume was calculated as follows: Volume = 0.5 × (tumor length) × (tumor width) 2 After euthanizing the mice, the heart, liver, spleen, lungs, and kidneys were harvested for histological observation, and tumors were sectioned for observation and immunohistochemical staining.

[0097] Figure 6 Photothermal imaging of mice after DTPTMI NPs were injected into them and the location was irradiated with laser for different durations.

[0098] Figure 7 The curve showing the change in tumor volume after DTPTMI NPs were injected into mice.

[0099] Figure 7 In this context, PBS represents phosphate buffer solution.

[0100] Figure 8 Immunofluorescence sections of tumor tissue.

[0101] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A photosensitive compound with near-infrared II aggregation-induced emission, characterized in that, The general structural formula is as follows: ； Where R1 is , , , , , , or ; R2 is , , , , or .

2. The photosensitive compound with near-infrared II aggregation-induced emission according to claim 1, characterized in that, The photosensitive compound containing near-infrared II aggregation-induced emission includes a compound with one of the following structural formulas: 。 3. A method for preparing a photosensitive compound with near-infrared II aggregation-induced emission as described in any one of claims 1-2, characterized in that, Includes the following steps: (1) Compound 1, compound 2, tetratriphenylphosphine palladium and potassium carbonate were mixed in a mixed solution of tetrahydrofuran and water and refluxed to obtain compound 3; (2) Compound 3 and compound 4 were mixed in acetic anhydride and reacted to obtain the photosensitive compound with near-infrared II aggregation-induced emission; Among them, compound 1 is Compound 2 is Compound 3 is Compound 4 is , , , , or .

4. The preparation method according to claim 3, characterized in that, The reaction was carried out at a temperature of 75°C for 8 hours in an oxygen-free atmosphere.

5. A type of near-infrared II aggregation-induced emission nanoparticle, characterized in that, It includes the photosensitive compound with near-infrared II aggregation-induced emission as described in any one of claims 1-2.

6. A method for preparing near-infrared II aggregation-induced emission nanoparticles as described in claim 5, characterized in that, The photosensitive compound with near-infrared II aggregation-induced emission was prepared into nanoparticles by nanoprecipitation or emulsification.

7. The use of a near-infrared II aggregation-induced emission photosensitive compound according to any one of claims 1-2 or the near-infrared II aggregation-induced emission nanoparticles according to claim 5 in the preparation of a photosensitizer for tumor phototherapy.

8. The application according to claim 7, characterized in that, The application is in the preparation of photosensitizers for phototherapy of hypoxic solid tumors.

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