A kind of light-activated tumor chemophotodynamic therapy diagnosis and treatment integrated nanomaterial and its preparation method and application

Abstract

The application discloses a kind of diagnosis and treatment integrated nano materials of photoactivation tumor chemophotodynamic therapy and its preparation method and application, the nano material, its structural formula is as shown in formula I: the nano material provided by the application can not only be used for near-infrared fluorescence imaging to tumor tissue, but also can release silver under the action of photoactivation, produce active oxygen, greatly enhance its antitumor effect, play the role of synergistic chemophotodynamic antitumor, and has great application prospect in tumor treatment.

Description

Technical Field

[0001] This invention relates to a multifunctional fluorescent molecular nanomaterial, its preparation method, and its application. Specifically, it relates to a fluorescent nanomaterial integrating chemistry and photodynamics, used for near-infrared imaging of tumor tissues, photoactivated chemotherapy, and photodynamic antitumor therapy, as well as its preparation method and application, belonging to the fields of organic synthesis and biomedicine. Background Technology

[0002] Cancer is one of the greatest threats to human life and health. Although radiotherapy, chemotherapy, and surgery are considered relatively effective treatments in clinical cancer care, many cancer patients experience adverse reactions after receiving radiotherapy and chemotherapy, especially with traditional chemotherapy drugs. This is because chemotherapy drugs lack selectivity, damaging normal cells and causing significant toxic side effects. Secondly, many chemotherapy drugs have low solubility in the body, resulting in low effective drug concentrations and ultimately low treatment rates. Furthermore, long-term misuse of chemotherapy drugs can lead to drug resistance in cancer cells, further contributing to unsatisfactory treatment outcomes.

[0003] Photodynamic therapy (PDT) has become a promising cancer treatment strategy due to its advantages such as spatiotemporal precision, minimal invasiveness, and lack of systemic side effects. It mainly consists of three elements: a light source, tissue oxygen, and a photosensitizer. As an important component of PDT, the photosensitizer (PSs) utilizes the energy absorbed by light irradiation to generate reactive oxygen species (ROS), which then react with nearby biomolecules such as DNA, proteins, and nucleic acids to kill cancer cells. Compared to traditional chemotherapy and radiotherapy, PDT uses localized exogenous light to activate its therapeutic activity, thus exhibiting strong selectivity and lower side effects. However, PDT also has some drawbacks: (1) the photosensitizer has low selectivity in biological tissue distribution, making it difficult to efficiently accumulate in tumors; (2) as local oxygen in the tumor tissue is consumed, the tumor enters a hypoxic environment, thus terminating the production of singlet oxygen and limiting its therapeutic effect. These two points greatly limit the potential application of PDT in clinical practice. Therefore, it is urgent to develop a novel synergistic treatment strategy by combining PDT with other treatment methods.

[0004] The development of nanotechnology has provided strong support for solving this problem. On the one hand, by encapsulating multiple drugs or anti-tumor active ingredients, multiple anti-tumor activities can be achieved; on the other hand, through the rational modification of nanomaterials, their tumor targeting and retention time can be enhanced, thereby improving the therapeutic effect of tumors. Furthermore, by integrating multimodal and multi-material approaches, synergistic treatment of tumors can be achieved, enhancing the therapeutic effect while reducing drug resistance in tumor cells and individual toxic side effects. Therefore, synergistic treatment strategies combining nanomaterials, chemotherapy, and photodynamic therapy have emerged. This design not only solves the problems of low tumor enrichment rate and short retention time of photosensitizers, but also achieves synergistic effects by leveraging the unique optical properties of nanostructures. Currently, the structures of silver carbene compounds covalently bound to photosensitizers are still rarely reported. Developing more compounds with excellent near-infrared fluorescence imaging will provide more possibilities for the design of synergistic photodynamic therapy strategies. Summary of the Invention

[0005] This invention addresses the limitation of the antitumor activity of traditional photodynamic materials in vivo, proposing a therapeutic nanomaterial for photoactivated chemophotodynamic therapy of tumors, along with its preparation method and applications. Through rational molecular design, it innovatively introduces photoactivated silver release to enhance antitumor activity and utilizes DSPE-PEG. 2000 Encapsulation of stable nanomaterial formulations improves the stability of molecules during in vivo metabolism, prolongs the residence time of molecules at tumor sites, and enhances chemophotodynamic antitumor activity.

[0006] The technical means adopted by this invention to solve the above problems is: a therapeutic nanomaterial for photoactivated tumor chemophotodynamic therapy, the structural formula of which is shown in Formula I: , Formula I, Among them, R1 and R2 are each one of hydrogen, alkyl, alkoxy, hydroxy, amino, dimethylamino and their derivatives; R3 is CH3COOAg or AgX (X=Cl, Br or I).

[0007] Preferably, the nanomaterial has the following structural formula: ' TPIMBS.

[0008] A method for preparing a therapeutic nanomaterial for photo-activated chemophotodynamic therapy of tumors, comprising the following synthesis steps: (1) Compound 1 and 4,7-dibromo-2,1,3-benzothiadiazole were dissolved in an organic solvent. Under inert gas protection and anhydrous conditions, 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride reagent (0.01-0.05 eq) was added dropwise. After the addition was complete, the mixture was heated and stirred in an oil bath at a set temperature. After the reaction was complete, the reaction solvent was distilled under reduced pressure and purified by column chromatography to obtain compound 2. The synthetic route is as follows: ; Compound 1 is triphenylamine 4-borate and its derivatives; the organic solvent is a solution of tetrahydrofuran and methanol (THF:MeOH=2:1, v / v), and the molar volume ratio of compound 1 to solvent is (1~2):10 mmol / mL; the molar ratio of compound 1 to 4,7-dibromo-2,1,3-benzothiadiazole is 1:(1~1.5); the amount of 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride reagent is 1 / 1000 to 1 / 1000 of the molar amount of compound 1; the reaction temperature is 90℃; the heating reaction time is 8~10 h; the eluent for column chromatography separation and purification is petroleum ether / dichloromethane=5 / 1, v / v.

[0009] (2) Compound 2 was dissolved in an organic solvent, imidazole was added, and the mixture was refluxed under set temperature and stirring conditions. After the reaction was completed, the reaction system was extracted with ethyl acetate multiple times, the organic layers were combined, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain compound 3. The synthetic route is as follows: ; The organic solvent is one or a mixture of N,N-dimethylformamide and dimethyl sulfoxide. The molar volume ratio of compound 2 to the organic solvent is 1:(1~5) mmol / mL. The molar ratio of compound 2 to imidazole is 1:(1.2~1.5). The reaction temperature is 160℃ and the heating reaction time is 8~10 h. The eluent for column chromatography separation and purification is dichloromethane / methanol = 20 / 1, v / v.

[0010] (3) Compound 3 was dissolved in an organic solvent, and then benzyl halide was added. The mixture was refluxed at a set temperature (100~110℃) and under stirring. After the reaction was completed, the reaction system was extracted with ethyl acetate multiple times. The organic layers were combined, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain compound 4. The synthetic route is as follows: ; The organic solvent is one or more of acetonitrile, N,N-dimethylformamide or dimethyl sulfoxide, the molar volume ratio of compound 3 to organic solvent is 1:(3~8) mmol / mL, the molar ratio of compound 3 to benzyl halide is 1:(1.2~1.5), the reaction temperature is 100~110 ℃, and the heating reaction time is 10~12 h; the eluent for column chromatography separation and purification is dichloromethane / methanol=10 / 1, v / v.

[0011] (4) Compound 4 was dissolved in an organic solvent, and silver oxide or silver acetate was added. The mixture was stirred at room temperature. After the reaction was completed, the product was purified to obtain a compound with the TPIMBS structure. The reaction formula is as follows: ; The organic solvent is one or more of dichloromethane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide or dimethyl sulfoxide, and the molar volume ratio of compound 4 to the organic solvent is 1: (5~20) mmol / mL; the molar ratio of compound 4 to silver oxide is 1: (1~1.5), or the molar ratio of compound 4 to silver acetate is 1: (2~4.5); the reaction time is 6~10 h; the purification process is as follows: after filtration, the filter residue is washed with dichloromethane, the filtrate is collected and the solvent is evaporated under reduced pressure.

[0012] The application of a therapeutic nanomaterial for photoactivated tumor chemophotodynamic therapy enables precise photodiagnosis of cancer and real-time monitoring of cancer treatment through its excellent near-infrared emission and AIE properties.

[0013] The beneficial effects of this invention are: 1. The preparation method of the chemical photodynamic synergistic anti-tumor nanomaterials provided by the present invention is simple, the raw materials are cheap and readily available, the synthesis process is simple, the separation and purification are easy, the yield is high, and it is suitable for large-scale production and widespread application.

[0014] 2. This material exhibits aggregation-induced emission, which can effectively avoid interference from self-absorption and background fluorescence of biological samples, and can be used for near-infrared fluorescence imaging of tumors.

[0015] 3. The nanomaterials provided by this invention can not only perform near-infrared fluorescence imaging of tumor tissues, but also release silver and generate reactive oxygen species under photoactivation, which greatly enhances their anti-tumor effect and plays a synergistic role in chemophotodynamic anti-tumor action, showing great application prospects in tumor treatment. Attached Figure Description

[0016] Figure 1 The AIE effect spectra of compounds TPIMB and TPIMBS from Example 2 are shown. Figure 2The UV absorption spectra of compounds TPIMB and TPIMBS from Example 3 after being irradiated with white light for different times are shown. Figure 3 This is a graph showing the MTT results of TPIMB / TPIMBS in Example 4; Figure 4 This is a live tumor imaging image of an animal using TPIMBS in Example 5; Figure 5 Images of the major organs and tumors isolated from the animal in Example 6 using TPIMBS. Figure 6 The in vivo antitumor results of TPIMBS in Example 7; Figure 7 The results of H&E staining of major organs and tissues isolated from the TPIMBS animal experiment in Example 8; Figure 8 The results of the TPIMBS in vitro hemolysis test in Example 9 are shown. Detailed Implementation

[0017] The invention will be further described below with reference to the accompanying drawings. Example 1

[0018] This example describes the synthesis of the compound TPIMBS. Synthesis of compound 2 with R1=H and R2=H Triphenylamine 4-borate (578 mg, 2.00 mmol) and 4,7-dibromo-2,1,3-benzothiadiazole (588 mg, 2 mmol) were dissolved in a mixture of tetrahydrofuran and methanol (10 mL tetrahydrofuran and 5 mL methanol) in a reaction flask. Under nitrogen protection and anhydrous conditions, 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride reagent (0.01 eq) was added dropwise. After the addition was complete, the mixture was heated and stirred in an oil bath at 90 °C for 8 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solvent was distilled under reduced pressure, and the mixture was purified by silica gel column chromatography using a mixture of petroleum ether and dichloromethane as the eluent (petroleum ether / dichloromethane = 5 / 1, v / v) to give compound 2 as an orange-red solid powder (727 mg, yield: 80%).

[0019] Synthesis of compound 3 with R1=H and R2=H Compound 2 (727 mg, 1.60 mmol) and imidazole (130 mg, 1.92 mmol) were dissolved in 4 mL DMF in a reaction flask. Anhydrous K₂CO₃ (287 mg, 2.08 mmol) and CuSO₄•5H₂O (80 mg, 0.32 mmol) were added, and the mixture was heated and stirred in an oil bath at 160 °C for 10 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was poured into 200 mL of water and extracted with ethyl acetate. The ethyl acetate layer was collected, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography using a mixture of dichloromethane and methanol as the eluent (dichloromethane / methanol = 20 / 1, v / v) to give compound 3 as a red viscous solid (320 mg, yield: 72%).

[0020] Synthesis of compound 4 (TPIMB) with R1=H, R2=H, and X=bromine Compound 3 (223 mg, 0.50 mmol) and benzyl bromide (128 mg, 0.75 mmol) were dissolved in 4 mL of DMF in a reaction flask and heated and stirred in an oil bath at 100 °C for 10 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was poured into 200 mL of water and extracted with ethyl acetate. The ethyl acetate layer was collected, the solvent was removed by vacuum distillation, and the solution was purified by silica gel column chromatography with a mixture of dichloromethane and methanol as the eluent (dichloromethane / methanol = 10 / 1, v / v) to give compound TPIMB as a red viscous solid (215 mg, yield: 70%).

[0021] Synthesis of compound TPIMBS Compound TPIMB (92 mg, 0.15 mmol) and silver oxide (42 mg, 0.18 mmol) were dissolved in 2 mL of dichloromethane and stirred at 25 °C for 6 hours in the dark. The reaction was monitored by TLC. After the reaction was complete, the mixture in the reaction flask was filtered under light-protected conditions. The filter residue was washed with dichloromethane, and the filtrate was collected. The solvent was removed by evaporation under reduced pressure to obtain the fluorescent probe TPIMBS as a red viscous solid (103.5 mg, yield: 95.8%).

[0022] The entire synthetic route is as follows: . Example 2

[0023] This embodiment verifies the AIE effect of the compound TPIMB / TPIMBS. Accurately weigh the compound TPIMB / TPIMBS prepared in Example 1, add it to a 50 mL volumetric flask, add deionized water to fully dissolve and dilute to volume, and shake well to obtain a 1 mM probe stock solution. Prepare solutions of water and tetrahydrofuran in different proportions (100:0, 90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80, 10:90, 5:95, 0:100), and add the probe stock solution to these solutions to accurately prepare a 10 μM probe solution. Measure its fluorescence emission intensity at 655 nm. Figure 1 As shown, with the increase of tetrahydrofuran content in the solvent, the fluorescence emission intensity of the fluorescent probe TPIMB / TPIMBS gradually increases at 650 nm. When the tetrahydrofuran content is 95%, there is a sudden change in fluorescence intensity. The fluorescence emission intensity reaches its strongest when the tetrahydrofuran content is 100%, indicating that the compound TPIMB / TPIMBS has a significant AIE effect. Example 3

[0024] This example describes the determination of the singlet oxygen generation capacity of the compound TPIMB / TPIMBS. Accurately weigh the compound TPIMB / TPIMBS prepared in Example 1 and dissolve it in DMSO to obtain a 2 mM TPIMB / TPIMBS solution. Add 50 μL each of the 2 mM TPIMB / TPIMBS solution and the 20 mM 9,10-anthratrium-di(methylene)dimalonic acid (ABDA) solution to 9.9 mL of deionized water to prepare working solutions containing 10 μM TPIMB / TPIMBS and 100 μM ABDA. Divide the working solutions into 10 groups, each group subjected to white light (25 mW / cm²). 2 The UV-Vis absorption spectra of each group of samples were measured after irradiation for different times (0s, 30s, 60s, 2min, 5min, 10min, 20min, 30min, 45min, 60min). The measurement results are as follows: Figure 2 As shown, the absorbance of the working solution at 358 nm, 378 nm and 400 nm gradually decreased with the extension of illumination time, indicating that TPIMB / TPIMBS has a significant singlet oxygen generation capacity. Example 4

[0025] This example demonstrates the MTT assay for the compound TPIMB / TPIMBS. MCF-7, 4T1, and MDA-MB-231 cells were seeded in 96-well plates and cultured overnight at 37 °C and 5% CO2. Then, solutions of TPIMB and TPIMB NPs were added to the cells, and the cells were co-cultured for 24 hours. For the irradiation group, cells were irradiated with white light (60 mW cm⁻¹) after 4 hours of co-culture. -2 After that, the cells were cultured for another 20 hours. Then, MTT solution (5 mg / mL) was added to the cells. -1 Cells were then cultured for another 4 hours. Subsequently, DMSO (150 μL) was used instead of the culture medium, and absorbance at 570 nm was measured using a microplate reader to analyze cell viability. Figure 3 As shown, under light-protected conditions, low doses (<1 μg / mL) -1 The TPIMB / TPIMBS NPs showed almost no cytotoxicity, with cell viability exceeding 90%. However, cytotoxicity increased significantly with increasing concentration, reaching a peak at 10 μg / mL. -1 At this time, cell viability was approximately 40%. These results indicate that high doses of TPIMB / TPIMBS NPs still possess antitumor activity despite the lack of light induction. When the concentration of TPIMB / TPIMBS NPs was 10 μg / mL... -1 At that time, white light (60 mWcm) -2 Irradiation significantly inhibited tumor growth, with cell survival rates <10%. These data indicate that TPIMBS NPs exhibited high cytotoxicity against various cancer cell lines after irradiation. Notably, TPIMBS NPs showed stronger cytotoxicity than TPIMB NPs under both dark and light conditions, suggesting that the presence of Ag in the molecule enhanced its antitumor activity. Example 5

[0026] This example demonstrates the use of TPIMBS in animal live tumor imaging. To investigate tumor accumulation and retention in vivo, BALB / c nude mice with tumors (n = 3) were anesthetized and then injected via the tail vein with an aqueous solution of TPIMBS NPs (100 μL, 1.0 mg / mL). -1 Fluorescence images were captured at different time points after injection (0, 12, 24, and 36 hours, respectively). The excitation wavelength was 550 nm, and signals at wavelengths from 600 to 700 nm were collected as emission signals. Figure 4 As shown, TPIMBS NPs began to exhibit near-infrared fluorescence 12 h after injection. The strong fluorescence emission of TPIMBS at the tumor site was retained for at least 36 h after injection, indicating that TPIMBS has a significant long-term tumor retention effect. Example 6

[0027] This example demonstrates the imaging assay of major organs and tumors isolated from animals using the compound TPIMBS. In this example, the mice that underwent in vivo imaging in Example 5 were euthanized. Major normal organs (heart, lungs, spleen, kidneys, and liver) and tumor tissue were removed and separated. After washing away surface blood with saline, the mice were placed in a glass dish for fluorescence image capture. The excitation wavelength was 550 nm, and signals at wavelengths of 600 to 700 nm were collected as emission signals. Figure 5 As shown, TPIMBS nanoparticles mainly emit strong fluorescence signals in tumor tissues, but only emit weak fluorescence in the liver and kidneys, indicating that the nanoparticles have obvious selective aggregation in tumors. Example 7

[0028] This example demonstrates the antitumor effect of the compound TPIMBS in animals. Mice were randomly divided into 4 groups (n = 6), including (1) intravenous injection of saline (100 μL) (control group); (2) intravenous injection of saline and light exposure (100 μL) (light exposure group); and (3) intravenous injection of TPIMB NPs (1 mg / mL). -1 v. TPIMBNPs (1 mg mL) -1 (100 μL) (TPIMB NPs); (4) Intravenous injection of TPIMB NPs with light irradiation (1 mg / mL) -1 (5) Intravenous injection of TPIMB NPs (1 mg / mL) (100 μL) (TPIMB NPs + Light). -1 (100 μL) (TPIMBS NPs); (6) Intravenous injection of TPIMBS NPs and light irradiation (1 mg mL) -1 100 μL (TPIMBS NPs + Light). The illumination for groups 4 and 6 was (150 mW cm⁻¹). 2 (15 minutes), administered intravenously within 24 hours after the injection of nanoparticles. The treatment involved saline solution and irradiation (150 mW cm⁻¹). 2 Mice in group (2) treated for 15 min served as negative controls. Tumor volume and mouse weight were measured every other day over 15 days. Major organs (heart, liver, spleen, lung, and kidney) and tumors were examined by H&E staining or TUNEL staining and observed under a fluorescence microscope (EVOS XL Core, Life Technologies, USA). Figure 6 As shown in Figure a, compared with the control group, all experimental groups showed significant tumor growth inhibition, consistent with the results of cell phototoxicity. Figure 6Figures b and c show isolated tumor photographs from different groups and the relative changes in tumor volume after different treatments, respectively. Notably, in the absence of light exposure, the relative tumor volume in the control group increased rapidly within 15 days. Conversely, the TPIMB / TPIMBS NPs-treated group without light exposure exhibited significant tumor suppression, indicating their superior ability to mediate cancer cell death through dark toxicity. It is noteworthy that after light exposure, TPIMB / TPIMBS NPs demonstrated a stronger killing effect on cancer cells, further inhibiting tumor growth and reflecting a more potent and significant inhibitory effect on tumor growth. Example 8

[0029] This example demonstrates the H&E staining assay of major organs in isolated animals treated with compound TPIMBS NPs. In this example, all mice in the six groups from Example 7 were euthanized on day 15 post-treatment. Major normal organs (heart, lungs, spleen, kidneys, and liver) were removed, sectioned, and stained. For H&E staining, tissues were immersed in 4% formalin solution, dehydrated, embedded in paraffin, and sectioned at a thickness of 6 micrometers. The H&E staining results are shown below. Figure 7 As shown, no obvious pathological changes were observed in any group, indicating that TPIMBS NPs have good biocompatibility. Example 9

[0030] This example describes the hemolysis test for the compound TPIMBS. Blood (2 mL) from healthy mice was donated by female mice. Red blood cells were collected by centrifugation at 10000g for 5 minutes, washed with normal physiological saline (0.9% NaCl) until the supernatant was clear, and resuspended in normal physiological saline (100 mL) to prepare a 2% red blood cell solution. Then, different concentrations (1, 5, 10, 20, 40, 60, 80, 100, 150, and 200 µg / mL) were prepared. -1 TPIMB and TPIMBS NPs were dissolved in normal physiological saline and an equal volume of 2% erythrocyte solution was added to centrifuge tubes. After incubation at 37°C for 2 hours, the supernatant was obtained by centrifugation at 10000g for 5 minutes and transferred to a 96-well plate. The absorbance at 540 nm was measured using a Multiskan FC microplate spectrophotometer (Thermo). Erythrocytes in normal physiological saline and deionized water were used as negative and positive controls, respectively. The following formula was used to calculate the percentage of hemolysis.

[0031] Hemolysis rate (%) = (sample absorbance - negative control absorbance) / (positive control absorbance - negative control absorbance) × 100.

[0032] The concentration of TPIMB and TPIMBS NPs solution reached 100 μg / mL.-1 No obvious hemolysis occurred at that time. Figure 8 This indicates that it has high biocompatibility with blood.

[0033] In the above embodiments, NPs refers to nanoparticles.

[0034] The above embodiments are for illustrative purposes only and are not intended to limit the invention. Those skilled in the art can make various changes or modifications without departing from the spirit and scope of the invention. Therefore, all equivalent technical solutions should also fall within the protection scope of the invention, which should be defined by the claims.

Claims

1. A therapeutic nanomaterial for photoactivated chemophotodynamic therapy of tumors, characterized in that: The structure is as follows: 。 2. A method for preparing the therapeutic nanomaterial for photoactivated tumor chemophotodynamic therapy as described in claim 1, characterized in that: The synthesis steps are as follows: (1) Compound 1 and 4,7-dibromo-2,1,3-benzothiadiazole were dissolved in an organic solvent. Under inert gas protection and anhydrous conditions, 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride reagent was added dropwise. After the addition was complete, the mixture was heated and stirred in an oil bath. After the reaction was complete, the reaction solvent was distilled under reduced pressure and purified by column chromatography to obtain compound 2, wherein R1, R2 and R3 are as described in claim 1. The synthetic route is as follows: ； (2) Compound 2 was dissolved in an organic solvent, imidazole was added, and the mixture was refluxed under heating and stirring. After the reaction was completed, the reaction system was extracted with ethyl acetate multiple times, the organic layers were combined, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain compound 3. The synthetic route is as follows: ； (3) Compound 3 was dissolved in an organic solvent, and benzyl bromide was added. The mixture was then refluxed at a set temperature of 100-110°C with stirring. After the reaction was completed, the reaction system was extracted multiple times with ethyl acetate. The organic layers were combined, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain compound 4, where X is bromine. The synthetic route is as follows: ； (4) Compound 4 was dissolved in an organic solvent, and silver oxide or silver acetate was added. The mixture was stirred at room temperature. After the reaction was completed, the product was purified to obtain a compound with the TPIMBS structure. The reaction formula is as follows: 。 3. The method for preparing the therapeutic nanomaterial for photo-activated tumor chemophotodynamic therapy as described in claim 2, characterized in that: The organic solvent was a solution of tetrahydrofuran and methanol, and the molar volume ratio of compound 1 to the solvent was (1~2):10 mmol / mL; the molar ratio of compound 1 to 4,7-dibromo-2,1,3-benzothiadiazole was 1:(1~1.5); the amount of 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride reagent was 1 / 1000 to 1 / 1000 of the molar amount of compound 1; the reaction temperature was 90℃; and the heating reaction time was 8~10 h; the eluent for column chromatography separation and purification was petroleum ether / dichloromethane = 5 / 1, v / v.

4. The method for preparing the therapeutic nanomaterial for photoactivated tumor chemophotodynamic therapy as described in claim 2, characterized in that: In step (2), the organic solvent is one or a mixture of N,N-dimethylformamide or dimethyl sulfoxide. The molar volume ratio of compound 2 to the organic solvent is 1:(1~5) mmol / mL, and the molar ratio of compound 2 to imidazole is 1:(1.2~1.5). The reaction temperature is 160℃, and the heating reaction time is 8~10 h. The eluent for column chromatography separation and purification is dichloromethane / methanol = 20 / 1, v / v.

5. The method for preparing the therapeutic nanomaterial for photoactivated tumor chemophotodynamic therapy as described in claim 2, characterized in that: In step (3), the organic solvent is one or more of acetonitrile, N,N-dimethylformamide or dimethyl sulfoxide, the molar volume ratio of compound 3 to organic solvent is 1:(3~8) mmol / mL, the molar ratio of compound 3 to benzyl bromide is 1:(1.2~1.5), the reaction temperature is 100~110 ℃, and the heating reaction time is 10~12 h; the eluent for column chromatography separation and purification is dichloromethane / methanol=10 / 1, v / v.

6. The method for preparing the therapeutic nanomaterial for photoactivated tumor chemophotodynamic therapy as described in claim 2, characterized in that: In step (4), the organic solvent is one or more of dichloromethane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide or dimethyl sulfoxide, and the molar volume ratio of compound 4 to organic solvent is 1: (5~20) mmol / mL; the molar ratio of compound 4 to silver oxide is 1: (1~1.5); and the reaction time is 6~10 h.

7. The method for preparing the therapeutic nanomaterial for photoactivated tumor chemophotodynamic therapy as described in claim 2, characterized in that: In step (4), the organic solvent is one or more of dichloromethane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide or dimethyl sulfoxide, and the molar volume ratio of compound 4 to the organic solvent is 1: (5~20) mmol / mL; the molar ratio of compound 4 to silver acetate is 1: (2~4.5); and the reaction time is 6~10 h.

8. The method for preparing the therapeutic nanomaterial for photoactivated tumor chemophotodynamic therapy as described in claim 2, characterized in that: The purification process in step (4) is as follows: after filtration, the filter residue is washed with dichloromethane, the filtrate is collected, and the solvent is evaporated under reduced pressure.

9. The application of the photo-activated tumor chemophotodynamic therapy nanomaterial of claim 1 in the preparation of reagents for photodiagnosis of cancer cells.

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