BODIPY-based photosensitizer compounded platinum complex as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biological medicine, and relates to a BODIPY-based photosensitizer compounded platinum complex, a preparation method and application thereof, the BODIPY-based photosensitizer compounded platinum complex comprises a cis-platinum complex c-BBP or a counter-platinum complex t-BBP, the molecular formula of the cis-platinum complex c-BBP and the counter-platinum complex t-BBP is C36H42B2F4N8Pt, the molecular formula of the counter-platinum complex c-BBP is C36H42B2F4N8Pt, and the molecular formula of the counter-platinum complex t-BBP is C36H42B2F4N8Pt. The platinum complex is combined with a BODIPY photosensitizer and combined with PDT, the defects of platinum drugs are effectively overcome, the complex has an inhibiting effect on tumor cells, and a new direction is provided for development of new anti-cancer drugs.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and particularly relates to a platinum complex of a BODIPY-based photosensitizer, a preparation method and application thereof in the preparation of photodynamic anti-tumor agents. Background Art

[0002] Malignant tumors are a difficult disease to overcome in today's society. The number of cancer cases reported in both developed and developing countries is increasing. It has become a complex systemic disease that affects human health and threatens life.

[0003] The anti-tumor effect of cisplatin is a major discovery in clinical cancer treatment. Platinum anticancer drugs represented by cisplatin play an important role in the treatment of various solid tumors. However, their application is largely affected by drug resistance and side effects, so cisplatin drugs need to be modified. Currently, cisplatin modified drugs mainly include: divalent platinum complexes, tetravalent platinum complexes and trans-platinum complexes.

[0004] Photodynamic therapy (PDT) has been playing a positive role in contemporary medicine, bringing new hope to the treatment of many diseases. PDT mainly relies on the photodynamic effect, which can kill tumor cells by toxicity to tumors, disrupting blood supply, and activating the immune system. And it can selectively treat specific tissues to avoid damaging healthy areas, so it has less lethality to normal tissues. Compared with surgical treatment, it also has the advantages of non-invasiveness and simple operation.

[0005] Photodynamic therapy is a new treatment method that interacts with light source, oxygen and various photosensitizers, so light source, molecular oxygen and photosensitizer are its three essential elements. As a classic photosensitizer, boron dipyrrolidone (BODIPY) complexes have good biocompatibility and stability, so they have attracted widespread attention. Platinum complexes are combined with BODIPY photosensitizers and used in combination with PDT in an attempt to effectively overcome the shortcomings of platinum drugs.

[0006] In the prior art, the Chinese patent specification with publication number CN114940691A discloses a bifunctional cisplatin derivative cBBP containing a fluorescent group, cis-bis(fluoroboron dipyrrole)-methylenepyridine-diaminoplatin (II) nitrate (cBBP) made of fluorescent molecules, aromatic heterocycles and cisplatin, which has good photodynamic bactericidal effect and certain drug resistance. In order to solve the current tumor treatment problems faced by humans, the structure of cBBP is modified, hoping that it can also play a good role in the field of anti-tumor. Summary of the invention

[0007] Aiming at the application and demand of platinum drugs in photodynamic therapy, the present invention further provides a platinum complex drug composited with a BODIPY-based photosensitizer with excellent cytotoxicity on the basis of the above-mentioned cisplatin derivative cBBP, which has good resistance to tumor cells under photodynamic targeted excitation.

[0008] The present invention first provides a BODIPY-based photosensitizer-complexed platinum complex, characterized in that it includes a cisplatin complex c-BBP or a trans-platinum complex t-BBP, and the structural formulas of the cisplatin complex c-BBP and the trans-platinum complex t-BBP are respectively: .

[0009] The method for preparing the above-mentioned BODIPY-based photosensitizer-compounded platinum complex drug of the present invention is characterized by comprising the following reaction process: .

[0010] Furthermore, the specific preparation steps of the above reaction process are: Step 1) Dissolve 2, 4-dimethylpyrrole and 4-formylpyridine in dichloromethane solution under nitrogen protection, stir at room temperature for 24 hours under the catalysis of trifluoroacetic acid, and track the reaction by TLC. After the reaction is completed, continue to drop THF solution containing DDQ into the reaction solution under ice bath conditions and continue stirring for 30 to 40 minutes, then add triethylamine and boron trifluoride ether to the reaction solution in sequence, and continue stirring for 10 to 12 hours at 0°C; after the reaction is completed, quench the reaction solution with pure water, extract and wash the reaction solution with dichloromethane, dry the collected organic phase with anhydrous sodium sulfate, remove the solvent by reduced pressure rotation, and separate by column chromatography to obtain dark red solid 4-pyridine BODIPY; Step 2) Dissolve cis-diamminedichloroplatinum or trans-diamminedichloroplatinum and AgNO3 in DMF respectively, react at 50-60°C for 24-30 h, centrifuge the solution and take the supernatant, add 4-pyridine BODIPY obtained in step 1) respectively, continue to react at 50-60°C for 24-30 h, add the reaction solution into ether for recrystallization, centrifuge and take the precipitate, wash it with methanol 2-3 times, and dry it to obtain the products c-BBP and t-BBP respectively.

[0011] Furthermore, in step 1), the molar ratio of 2, 4-dimethylpyrrole, 4-formylpyridine and DDQ is 20-22:10:10-15, the volume mass ratio of trifluoroacetic acid to 2, 4-dimethylpyrrole is 0.05 mL / g, and the volume ratio of ethylamine and boron trifluoride relative to the molar ratio of 2, 4-dimethylpyrrole is 0.20-0.25 mL / mmol.

[0012] In order to prepare the cisplatin complex by separation, when preparing the cisplatin complex c-BBP in step 2), Dissolve cis-diamminedichloroplatinum and AgNO3 in DMF respectively, react at 50-60°C for 24-30h, centrifuge the solution, take the supernatant and add 4-pyridine BODIPY prepared in step 1, continue to react at 50-60°C for 24-30h, add the reaction solution into ether for recrystallization, take the precipitate after centrifugation, wash it with methanol 2-3 times, and dry it to obtain the product c-BBP.

[0013] To facilitate the further preparation of the anti-platinum complex, the anti-platinum complex c-BBP is prepared in step 2), trans-dichlorodiammineplatinum and AgNO3 are dissolved in DMF respectively, reacted at 50-60°C for 24-30h, and then the solution is centrifuged and the supernatant is added to the 4-pyridine BODIPY prepared in step 1, and the reaction is continued at 50-60°C for 24-30h, and the reaction solution is added to ether for recrystallization, and the precipitate is taken after centrifugation, and then washed with methanol 2-3 times, and dried to obtain the product c-BBP.

[0014] Furthermore, the molar ratio of the platinum complex, AgNO3 and 4-pyridine BODIPY is 1:2:2.

[0015] The BODIPY-based platinum drug complexes c-BBP and t-BBP of the present invention have beneficial effects: Compared with the original cis-trans platinum, BODIPY-based complex platinum drugs increase cell permeability, and the hydrophobicity of the modified groups reduces the probability of DNA damage repair; By modifying BODIPY photosensitizer on platinum drugs, platinum drugs can have the effect of photodynamic therapy. The reactive oxygen species (ROS) generated by the photodynamic effect can overcome the drug resistance of platinum drugs. Platinum drugs combined with photosensitizers have significantly better killing effects on tumor cells than original platinum drugs, and can be activated by light. They have higher toxicity to tumor cells under light conditions, but lower toxicity under dark conditions, ensuring biosafety. Tests have shown that the proportion of hydroxyl radicals in the reactive oxygen species generated by the platinum-drug composite photosensitizer under light is relatively high, and it is not highly dependent on oxygen, making it more suitable for use in the hypoxic microenvironment of tumors. After platinum drugs were combined with photosensitizers, they still showed properties similar to those of the original cis-trans platinum. The anti-tumor effect of the cis-complex c-BBP was significantly higher than that of the trans-complex t-BBP. The cis complex c-BBP can be localized in mitochondria in tumor cells and has a higher oxygen production efficiency; The cis-complex c-BBP complex has higher cytotoxicity than the previously developed cBBP complex and better anti-tumor effect.

[0016] The present invention also provides an application of the platinum complex compounded with the BODIPY-based photosensitizer in the preparation of a drug for inhibiting cancer cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The hydrogen nuclear magnetic resonance spectra of c-BBP and t-BBP prepared in the first embodiment of the present invention are shown.

[0018] Figure 2 The light intensity of the full spectrum light source is 40mW / cm2 at 400-800nm 2 Fluorescence intensity change diagram of DCFH solution (concentration 10 μg / mL) with fluorescence intensity measured every 30 seconds under irradiation.

[0019] Figure 3 Full spectrum light source with a light intensity of 400-800nm ​​and a light intensity of 40mW / cm 2 The fluorescence intensity change of the ABDA solution (concentration of 10 μg / mL) with UV absorption was measured every 30 seconds under irradiation.

[0020] Figure 4 The light intensity of the full spectrum light source is 40mW / cm2 at 400-800nm 2 Fluorescence intensity change diagram of DHR123 solution (concentration 10μg / mL) with fluorescence intensity measured every 1min under irradiation.

[0021] Figure 5 The light intensity of the full spectrum light source is 40mW / cm2 at 400-800nm 2 Fluorescence intensity change diagram of HPF solution (concentration 10μg / mL) with fluorescence intensity measured every 1min under irradiation.

[0022] Figure 6 c-BBP and t-BBP were incubated with Hela cells for 4 h at a full spectrum intensity of 400-800 nm at 40 mW / cm 2 Schematic diagram of using the CCK-8 kit to detect cell viability after 15 minutes of irradiation and continued incubation for 8 hours.

[0023] Figure 7 Schematic diagram of incubating Hela cells with c-BBP and t-BBP for 12 hours and detecting cell viability using the CCK-8 kit.

[0024] Figure 8 c-BBP and t-BBP were incubated with P02 cells for 4 h, and the full spectrum light intensity was 40 mW / cm in the range of 400-800 nm. 2 Schematic diagram of using the CCK-8 kit to detect cell viability after 15 minutes of irradiation and continued incubation for 8 hours.

[0025] Fig. 9 Schematic diagram of incubating P02 cells with c-BBP and t-BBP for 12 hours and detecting cell viability using the CCK-8 kit.

[0026] Fig.10 c-BBP and cBBP were incubated with P02 cells for 8 h at a full spectrum intensity of 400-800 nm at 40 mW / cm 2 Schematic diagram of detecting cell viability using the CCK-8 kit after irradiation for 30 minutes and continuing to incubate for 8 hours.

[0027] Fig.11 This is the co-localization confocal fluorescence imaging of c-BBP and t-BBP after they were co-incubated with P02 cells for 30 minutes and then with Mitotracker (mitochondrial dye) for 30 minutes. DETAILED DESCRIPTION Example 1 Complex Synthesis

[0028] In this embodiment, BODIPY-based platinum drug complexes c-BBP and t-BBP were prepared, both of which have the molecular formula C 36 H 42 B2F4N8Pt, the chemical structures are: .

[0029] The above BODIPY-based platinum drug complex is prepared by the following steps: Under nitrogen protection, add a drop of trifluoroacetic acid to a dichloromethane solution (150 ml) containing 2, 4-dimethylpyrrole (2.0 g, 21 mmol) and 4-formylpyridine (1.2 g, 10 mmol), stir at room temperature for 24 h, and track the reaction by TLC. After the reaction is completed, add 50 mL of THF solution containing DDQ (13 mmol, 2.5 g) to the reaction solution under ice bath conditions and continue stirring for 30 minutes. Then, add 5 mL of triethylamine and 5 mL of boron trifluoride ether to the reaction solution in sequence, and continue stirring overnight at 0°C. After the reaction is completed, add 100 mL of water and 100×2 mL of dichloromethane to the reaction solution. After the organic phase is dried over anhydrous sodium sulfate, the solvent is removed by vacuum rotation, and a dark red solid of 0.7 g is obtained after separation by column chromatography, which is 4-pyridine BODIPY.

[0030] The product 4-pyridine BODIPY was characterized by NMR, and the specific NMR characterization was Yield: 20%. 1H NMR (CDCl3, ppm): δ8.72-8.70(d,2H,J=6Hz),7.32-7.30(d,2H,J=6Hz),6.0(s,2H),2.56(s,6H,),1.48(s,6H).

[0031] Cis-diamminedichloroplatinum, trans-diamminedichloroplatinum and AgNO3 were dissolved in DMF respectively, reacted at 50°C for 24 hours, the solution was centrifuged, the supernatant was added with 4-pyridine BODIPY, and the reaction was continued at 50°C for 24 hours. The reaction solution was added into ether for recrystallization, the precipitate was taken after centrifugation, and then washed with methanol for 2-3 times and dried to obtain the products c-BBP and t-BBP respectively.

[0032] like Figure 1 The following are the hydrogen nuclear magnetic resonance spectra of the products c-BBP and t-BBP, which prove the successful synthesis and correct structure of the two complexes. Example 2 Detection of oxygen-active capacity of complex

[0033] In this example, the c-BBP and t-BBP prepared in Example 1 were subjected to photodynamic detection using DCFH, DHR123, ABDA and HPF fluorescent probes, and the yields of various types of reactive oxygen species were calculated. In the photodynamic detection, cytotoxicity and cell imaging experiments, the c-BBP and t-BBP samples were prepared into a 1 mg / ml solution as the sample solution, and the solvent was DMSO:H2O=1:9 1.DCFH detection First, add 0.5ml of 1mM DCFH-DA ethanol solution to 2ml of 0.01N NaOH and stir at room temperature for 30min; then adjust the pH of the solution with 10ml of 25mM pH=7.4 PBS to about 7 for later use. During the test, take 10μl of c-BBP and t-BBP sample solutions (1mg / ml) and add them to 990μl of the prepared DCFH solution respectively. After mixing, take 100μl of the mixed solution and drop it into a 96-well plate respectively. Use an enzyme-labeled instrument to measure the fluorescence intensity at 0s and use 400-800nm ​​(40mW / cm 2 ) full spectrum light source, record the value every 30 seconds, and measure until 5 minutes. The results are as follows Figure 2 As shown, the fluorescence intensity of c-BBP increased by about 9 times compared with that of DCFH solution, while that of cBBP increased by about 21 times compared with that of DCFH solution, which proved that the total amount of reactive oxygen species of cBBP was higher than that of c-BBP, and the total amount of reactive oxygen species of the two trans complexes was lower than that of the two cis complexes.

[0034] ABDA testing Dissolve 1 mg ABDA in 97 μl DMSO to obtain ABDA DMSO solution. Take 2 μl ABDA DMSO solution and add it to 1 ml c-BBP and t-BBP sample solutions respectively. Measure the UV absorbance at 200-800 nm at 0 s with an ELISA reader. Then use 400-800 nm (40 mW / cm 2 The sample was irradiated with a full-spectrum light source and the value was recorded every 30 seconds. The singlet oxygen yield of the sample was calculated based on the decrease in absorbance at 358nm, 378nm and 400nm. The results are shown in Figure 3 As shown, taking Rose Bengal (RB) as reference, the singlet oxygen yield of c-BBP was 55.8%, and the singlet oxygen yield of cBBP was 70.1%, which proved that the reactive oxygen species produced by cBBP were mainly singlet oxygen, which belonged to type II photosensitizer, while the reactive oxygen species produced by c-BBP were more superoxide radicals and hydroxyl radicals, which belonged to type I photosensitizer.

[0035] DHR123 detection 10 μl of c-BBP and t-BBP sample solutions were added to 990 μl of dihydrorhodamine 123 (DHR123), a superoxide anion detection reagent, and the samples were illuminated at 400-800 nm (40 mW / cm 2 The fluorescence intensity was measured in a fluorescence spectrophotometer, with the value recorded every 1 min, and the measurement lasted for 5 min. Figure 4 As shown, the ability of c-BBP and t-BBP molecules to produce superoxide anions is similar, which is 15.6 times and 15.7 times that of the blank control group, respectively. At the same time, the ability of c-BBP and t-BBP molecules to produce superoxide anions is also higher than that of cBBP and tBBP under the same solution conditions.

[0036] HPF Testing Hydroxyl free radical detection reagent hydroxyphenylfluorescein (HPF) was prepared into a 10 mM DMSO stock solution. 10 μl of c-BBP and t-BBP sample solutions were added to 990 μl of 5 μM HPF in PBS solution, respectively. 2 The fluorescence intensity was measured in a fluorescence spectrophotometer, with the value recorded every 1 min, and the measurement lasted for 5 min. Figure 5As shown, the ability of c-BBP molecules to produce hydroxyl radicals is significantly higher than that of t-BBP molecules. The ability of c-BBP molecules to produce hydroxyl radicals can reach 15.7 times that of the blank control group, while the ability of t-BBP molecules to produce hydroxyl radicals is only 4.6 times that of the blank control group. Hydroxyl radicals have a strong oxidative ability among many reactive oxygen species. The high yield of c-BBP molecules proves that they can cause greater damage to tumor cells. In addition, the process of producing hydroxyl radicals is not as dependent on oxygen as other reactive oxygen species. It can achieve a higher killing effect in the hypoxic microenvironment of the tumor. Similarly, the ability of c-BBP molecules to produce hydroxyl radicals is also higher than that of cBBP, and the ability of t-BBP molecules to produce hydroxyl radicals is also higher than that of tBBP. Example 3 Cytotoxicity Detection of Complexes

[0037] Cytotoxicity assay of pristine cistransplatin First, add 3 ml of trypsin digestion solution to the culture dishes of P02 cells (mouse pancreatic cancer cells) and Hela cells (human cervical cancer cells) and wait for 4 minutes. After digestion, put them into centrifuge tubes, take 10 μl to the cell counting plate for counting, centrifuge the cells and add culture medium to make a cell suspension with a cell count of 10w / ml. In a 96-well plate, spread 100 μl of P02 cells and Hela cells with a cell count of 10w / ml in each well and incubate for 24 hours. Add different concentrations of cisplatin and anti-platin to the cells and incubate for 24 hours, then add cck-8 and incubate for 1 hour. Use an enzyme reader to measure the absorbance of each well in the 96-well plate at 450nm to detect the cell survival rate. Under dark conditions, the IC value of cisplatin for P02 cells 50 The IC value for Hela cells is 6.3889 μg / mL. 50 The IC value of cisplatin for P02 cells under light conditions was 2.3899 μg / mL. 50 The IC value for Hela cells is 7.7734 μg / mL. 50 The IC values ​​of cisplatin for P02 cells and Hela cells were 3.5715 μg / mL, indicating that the original cisplatin had no special response to light and dark conditions, while the anti-platinum had a high IC values ​​for P02 cells and Hela cells regardless of light or dark conditions. 50 All of them were greater than 100 μg / mL, proving that the killing effect of anti-platinum on tumor cells was extremely low.

[0038] 2. Dark cytotoxicity assay of c-BBP and t-BBP First, add 3 ml of trypsin digestion solution to the P02 and Hela cell culture dishes and wait for 4 minutes. After digestion, put them into centrifuge tubes, take 10 μl to the cell counting plate for counting, centrifuge the cells and add culture medium to make a cell suspension with a cell count of 10w / ml. In a 96-well plate, spread 100 μl of P02 cells with a cell count of 10w / ml in each well and incubate for 24 hours. Add c-BBP and t-BBP sample solutions to the cells and incubate for 24 hours, then add cck-8 and incubate for 1 hour. Use an enzyme reader to measure the absorbance of each well in the 96-well plate at 450nm to detect the cell survival rate. The results are as follows: Figure 6 , 7 shows that under dark conditions, c-BBP molecules have an effect on the IC 50 The IC value for Hela cells is 54.4093 μg / mL. 50 The IC values ​​of t-BBP molecules on the two cell types were 19.1763 μg / mL, which had a killing effect on tumors. 50 Both are greater than 100μg / mL, similar to anti-platinum, and have extremely low tumor killing effects.

[0039] 3. c-BBP and t-BBP photocytotoxicity assay P02 and Hela cells were placed in 96-well plates and incubated for 24 hours. c-BBP and t-BBP sample solutions were added to the cells and incubated for 4 hours. The light intensity was 400-800nm ​​full spectrum at 40mW / cm 2 After irradiation for 15 min and continued incubation for 8 h, CCK-8 was added and incubated for 1 h. The absorbance of each well in the 96-well plate was measured at 450 nm using an ELISA instrument to detect the cell survival rate. The results were as follows: Figure 8 , 9 shows that under light conditions, c-BBP molecules have an effect on the IC 50 The IC value for Hela cells is 0.7623 μg / mL. 50 The IC of t-BBP on both cells was 0.6361 μg / mL, indicating that c-BBP has a strong killing effect on tumors under light conditions, indicating that light can greatly enhance the killing effect of c-BBP molecules on tumors, and the lower toxicity under dark conditions can ensure biosafety. 50 All of them were greater than 50μg / mL, and the tumor killing effect was still low.

[0040] 4. Comparison of photocytotoxicity between c-BBP and cBBP A 96-well plate with P02 cells was incubated for 24 h. The same concentrations of c-BBP and cBBP sample solutions were added. After the cells were incubated for 8 h, the light intensity was 400-800 nm in the full spectrum at 40 mW / cm 2After irradiation for 30 minutes, the cells were incubated for 8 hours, and then CCK-8 was added for 1 hour. The absorbance of each well in the 96-well plate was measured at 450 nm using an ELISA reader to detect the cell survival rate. The results were as follows: Fig.10 As shown, the cytotoxicity of the c-BBP molecule is significantly higher than that of the previous cBBP molecule, indicating that the c-BBP molecule has a higher anti-tumor effect.

[0041] Example 4 Complex Cell Co-localization Detection Add 2 ml of P02 cells with a cell count of 10w / ml to the confocal dish and incubate in the incubator for 24 hours. Add c-BBP and t-BBP sample solutions respectively, incubate for 30 minutes, wash with PBS, then add MitoTracker (mitochondrial fluorescent probe) and incubate again for 30 minutes, wash with PBS and add 2 ml PBS. Colocalization is performed on the confocal microscope. The results are shown in Fig.11 As shown, MitoTrack mitochondrial dye can locate the mitochondria of cells and exhibit red fluorescence, while c-BBP and t-BBP molecules fluoresce green. When the two are located in the same cell, they appear yellow. c-BBP can accurately locate the mitochondria in cells with a PCC (confocal coefficient) of 0.6, which can improve the oxygen production efficiency of the molecule, while t-BBP cannot be located in mitochondria with a PCC of 0.4.

Claims

1. A BODIPY-based photosensitizer-complexed platinum complex, characterized in that: It includes a cisplatin complex c-BBP or a trans-platinum complex t-BBP, wherein the molecular formula of the cisplatin complex c-BBP and the trans-platinum complex t-BBP is C 36 H 42 B2F4N8Pt, the structural formulas are: ； (c-BBP) ； (t-BBP).

2. A method for preparing the BODIPY-based photosensitizer-compounded platinum complex drug according to claim 1, characterized in that: The reaction process includes the following: 。 3. The preparation method according to claim 2, characterized in that: The specific preparation steps are: Step 1) Dissolve 2, 4-dimethylpyrrole and 4-formylpyridine in dichloromethane solution under nitrogen protection, stir at room temperature for 24 hours under the catalysis of trifluoroacetic acid, and track the reaction by TLC. After the reaction is completed, continue to drop THF solution containing DDQ into the reaction solution under ice bath conditions and continue stirring for 30 to 40 minutes, then add triethylamine and boron trifluoride ether to the reaction solution in sequence, and continue stirring for 10 to 12 hours at 0°C; after the reaction is completed, quench the reaction solution with pure water, extract and wash the reaction solution with dichloromethane, dry the collected organic phase with anhydrous sodium sulfate, remove the solvent by reduced pressure rotation, and separate by column chromatography to obtain dark red solid 4-pyridine BODIPY; Step 2) Dissolve cis-diamminedichloroplatinum or trans-diamminedichloroplatinum and AgNO3 in DMF respectively, react at 50-60°C for 24-30 h, centrifuge the solution and take the supernatant, add 4-pyridine BODIPY obtained in step 1) respectively, continue to react at 50-60°C for 24-30 h, add the reaction solution into ether for recrystallization, centrifuge and take the precipitate, wash it with methanol 2-3 times, and dry it to obtain the products c-BBP and t-BBP respectively.

4. The preparation method according to claim 3, characterized in that: In step 1), the molar ratio of 2, 4-dimethylpyrrole, 4-formylpyridine and DDQ is 20-22:10:10-15, the volume mass ratio of trifluoroacetic acid to 2, 4-dimethylpyrrole is 0.05 mL / g, and the volume ratio of ethylamine and boron trifluoride to the molar ratio of 2, 4-dimethylpyrrole is 0.20-0.25 mL / mmol.

5. The preparation method according to claim 3, characterized in that: When preparing the cisplatin complex c-BBP in step 2), Dissolve cis-diamminedichloroplatinum and AgNO3 in DMF respectively, react at 50-60°C for 24-30h, centrifuge the solution, take the supernatant and add 4-pyridine BODIPY prepared in step 1, continue to react at 50-60°C for 24-30h, add the reaction solution into ether for recrystallization, take the precipitate after centrifugation, wash it with methanol 2-3 times, and dry it to obtain the product c-BBP.

6. The preparation method according to claim 3, characterized in that: In step 2), the anti-platinum complex c-BBP is prepared by dissolving trans-dichlorodiammineplatinum and AgNO3 in DMF respectively, reacting at 50-60°C for 24-30h, centrifuging the solution, taking the supernatant and adding the 4-pyridine BODIPY prepared in step 1, and continuing to react at 50-60°C for 24-30h. The reaction solution is added to ether for recrystallization, centrifuging and taking the precipitate, washing it with methanol 2-3 times, and drying to obtain the product c-BBP.

7. The preparation method according to claim 5 or 6, characterized in that: The molar ratio of platinum complex, AgNO3 and 4-pyridine BODIPY is 1:2:

2.

8. Use of the BODIPY-based photosensitizer-complexed platinum complex according to claim 1 in the preparation of drugs for inhibiting cancer cells.

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