A platinum complex of BODIPY-based photosensitizer, its preparation method and its application

Abstract

This invention pertains to the field of biomedical technology and relates to a platinum complex composed of a BODIPY-based photosensitizer, its preparation method, and its application. The platinum complex composed of the BODIPY-based photosensitizer of this invention includes either the cisplatin complex c-BBP or the antiplatinum complex t-BBP, wherein the molecular formulas of the cisplatin complex c-BBP and the antiplatinum complex t-BBP are Ci. 36 H 42 B2F4N8Pt, by combining a platinum complex with BODIPY photosensitizer and using it in combination with PDT, effectively overcomes the shortcomings of platinum-based drugs. Furthermore, the complex has an inhibitory effect on tumor cells, providing a new direction for the development of new anticancer drugs.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medicine, and particularly relates to a platinum complex combined with a BODIPY-based photosensitizer, a preparation method thereof and application of the platinum complex in preparation of a photodynamic anti-tumor agent. BACKGROUND

[0002] Malignant tumor is a difficult problem in human diseases in today's society, and the number of cancer cases reported in developed and developing countries is increasing, which has become a systematic and complex disease affecting human health and endangering life.

[0003] The anti-tumor effect of cisplatin is a major discovery in clinical cancer treatment, and platinum-based 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, the modified cisplatin 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, and it has brought new hope for the treatment of various diseases. PDT relies on photodynamic effect to kill tumor cells by toxicity to tumors, disrupting blood supply, and activating the immune system. And it can selectively target specific tissues for treatment, thereby avoiding damage to healthy areas, so it has less damage to normal tissues. Compared with surgical treatment, it also has the advantages of non-invasive and simple operation.

[0005] Photodynamic therapy is a new treatment method that relies on the interaction of light sources, oxygen and various photosensitizers, so light sources, molecular oxygen and photosensitizers are the three essential elements. Fluoroboron dipyrrin (BODIPY) complexes, as classic photosensitizers, have good biocompatibility and stability, so they have received widespread attention. Combining platinum complexes with BODIPY photosensitizers and using them with PDT can 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 containing a fluorescent group, cis-bis-fluoroboron dipyrrin-methylene pyridine-diamine platinum (II) nitrate (cBBP) made of a fluorescent molecule, an aromatic heterocycle and cisplatin, which has good photodynamic bactericidal effect and certain drug resistance. In order to solve the current tumor treatment problem faced by mankind, the structure of cBBP is modified, and it is hoped that it can also play a good effect in the field of anti-tumor. SUMMARY

[0007] The application is directed to the application and demand in platinum drug photodynamic therapy, and further provides a BODIPY-based photosensitizer complexed platinum complex drug with excellent cytotoxicity, which has good resistance to tumor cells under the photodynamic targeting excitation on the basis of the above cisplatin derivative cBBP.

[0008] The application first provides a BODIPY-based photosensitizer complexed platinum complex, characterized by comprising cisplatin complex c-BBP or transplatin complex t-BBP, and the structural formulae of the cisplatin complex c-BBP and the transplatin complex t-BBP are as follows:

[0009]

[0010] The preparation method of the above BODIPY-based photosensitizer complexed platinum complex drug, characterized by comprising the following reaction process:

[0011]

[0012] Further, the specific preparation steps of the above reaction process are as follows:

[0013] Step 1) 2, 4-dimethylpyrrole and 4-aldehyde pyridine are dissolved in dichloromethane solution under nitrogen protection, stirred at room temperature for 24 h under the catalysis of trifluoroacetic acid, the reaction is tracked by TLC, after the reaction is completed, DDQ THF solution is continuously added to the reaction liquid under ice bath condition for 30-40 min, then triethylamine and boron trifluoride ether are sequentially added to the reaction liquid, and the stirring is continued at 0℃ for 10-12 h; after the reaction is completed, the reaction liquid is quenched with pure water, then the reaction liquid is extracted and washed with dichloromethane, the collected organic phase is dried over anhydrous sodium sulfate, the solvent is removed under reduced pressure, and the dark red solid 4-pyridine BODIPY is obtained after separation by column chromatography.

[0014] Step 2) cis-diamminedichloroplatinum or trans-diamminedichloroplatinum is respectively dissolved in DMF with AgNO3, and the solution is reacted at 50-60℃ for 24-30 h, the supernatant is taken after the solution is centrifuged, and then 4-pyridine BODIPY obtained in step 1) is added, and the reaction is continued at 50-60℃ for 24-30 h, the reaction liquid is added to ether for recrystallization, the precipitate is taken after centrifugation, and the precipitate is washed with methanol for 2-3 times, and then dried to obtain the products c-BBP and t-BBP.

[0015] Further, in step 1), the molar ratio of 2, 4-dimethylpyrrole, 4-aldehyde pyridine 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 amount of 2, 4-dimethylpyrrole is 0.20-0.25 mL / mmole.

[0016] In order to facilitate the preparation of cisplatin complexes, in step 2), when preparing cisplatin complex c-BBP,

[0017] Cis-dichlorodiammine platinum and AgNO3 are dissolved in DMF, respectively, and reacted at 50-60℃ for 24-30h, then the supernatant is taken after centrifugation, 4-pyridine BODIPY prepared in step 1 is added, and the reaction is continued at 50-60℃ for 24-30h, the reaction solution is added to ether for recrystallization, the precipitate is taken after centrifugation, and then washed with methanol for 2-3 times, and the product c-BBP is obtained after drying.

[0018] In order to facilitate the preparation of transplatin complexes, in step 2), when preparing transplatin complex c-BBP, trans-dichlorodiammine platinum and AgNO3 are dissolved in DMF, respectively, and reacted at 50-60℃ for 24-30h, then the supernatant is taken after centrifugation, 4-pyridine BODIPY prepared in step 1 is added, and the reaction is continued at 50-60℃ for 24-30h, the reaction solution is added to ether for recrystallization, the precipitate is taken after centrifugation, and then washed with methanol for 2-3 times, and the product c-BBP is obtained after drying.

[0019] Further, the molar amount ratio of platinum complex, AgNO3 and 4-pyridine BODIPY is 1:2:2.

[0020] The BODIPY-based platinum drug complex c-BBP of the application has the following advantages:

[0021] Compared with the original cisplatin and transplatin, the BODIPY-based complex platinum drug increases the cell permeability, and the hydrophobicity of the modified group reduces the probability of DNA damage repair;

[0022] By modifying the BODIPY photosensitizer on the platinum drug, the platinum drug can have the effect of photodynamic therapy, and the active oxygen species (ROS) generated by the photodynamic effect can overcome the drug resistance of the platinum drug;

[0023] The killing of tumor cells by the platinum drug complex photosensitizer is obviously superior to the original platinum drug, and the platinum drug complex photosensitizer can be activated by light, has higher toxicity to tumor cells under light, and has lower toxicity under dark conditions, which guarantees the biological safety;

[0024] The test proves that the proportion of hydroxyl radicals in active oxygen species generated by the platinum drug combined with the photosensitizer under light is high, and the dependence on oxygen is not high, and it is more suitable for the tumor hypoxic microenvironment.

[0025] The platinum drug combined with the photosensitizer still shows similar properties to the original cis-platinum, and the anti-tumor effect of the cis-complex c-BBP is obviously higher than that of the trans-complex t-BBP.

[0026] The cis-complex c-BBP can be positioned in mitochondria in tumor cells, and has higher oxygen production efficiency.

[0027] The cytotoxicity of the cis-complex c-BBP is higher than that of the previously developed cBBP complex, and the anti-tumor effect is better.

[0028] The application also provides a use of the platinum complex combined with the above-mentioned BODIPY-based photosensitizer in preparation of a drug for inhibiting cancer cells. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 The nuclear magnetic resonance hydrogen spectrum of c-BBP and t-BBP prepared in the first embodiment of the application.

[0030] Figure 2 The DCFH solution (concentration of 10 ug / mL) is measured every 30 s under the irradiation of the 400-800 nm full spectrum light source with an intensity of 40 mW / cm 2 The fluorescence intensity change graph of the DCFH solution (concentration of 10 ug / mL) is measured every 30 s under the irradiation of the 400-800 nm full spectrum light source with an intensity of 40 mW / cm

[0031] Figure 3 The DCFH solution (concentration of 10 ug / mL) is measured every 30 s under the irradiation of the 400-800 nm full spectrum light source with an intensity of 40 mW / cm 2 The fluorescence intensity change graph of the DCFH solution (concentration of 10 ug / mL) is measured every 30 s under the irradiation of the 400-800 nm full spectrum light source with an intensity of 40 mW / cm

[0032] Figure 4 The DCFH solution (concentration of 10 ug / mL) is measured every 30 s under the irradiation of the 400-800 nm full spectrum light source with an intensity of 40 mW / cm 2 The fluorescence intensity change graph of the DCFH solution (concentration of 10 ug / mL) is measured every 30 s under the irradiation of the 400-800 nm full spectrum light source with an intensity of 40 mW / cm

[0033] Figure 5 The DCFH solution (concentration of 10 ug / mL) is measured every 30 s under the irradiation of the 400-800 nm full spectrum light source with an intensity of 40 mW / cm 2 The fluorescence intensity change graph of the DCFH solution (concentration of 10 ug / mL) is measured every 30 s under the irradiation of the 400-800 nm full spectrum light source with an intensity of 40 mW / cm

[0034] Figure 6 The c-BBP and t-BBP are incubated with Hela cells for 4 h, and the 400-800 nm full spectrum light intensity is 40 mW / cm2 The schematic diagram for detecting cell survival rate using cck-8 kit after 8h incubation after 15min irradiation.

[0035] Figure 7 The schematic diagram for detecting cell survival rate using cck-8 kit after 12h incubation of c-BBP and t-BBP with HeLa cells.

[0036] Figure 8 The schematic diagram for detecting cell survival rate using cck-8 kit after 4h incubation of c-BBP and t-BBP with P02 cells under 40mW / cm2 light intensity of 400-800nm full spectrum. 2 The schematic diagram for detecting cell survival rate using cck-8 kit after 8h incubation after 15min irradiation.

[0037] Figure 9 The schematic diagram for detecting cell survival rate using cck-8 kit after 12h incubation of c-BBP and t-BBP with P02 cells.

[0038] Figure 10 The schematic diagram for detecting cell survival rate using cck-8 kit after 8h incubation of c-BBP and cBBP with P02 cells under 40mW / cm2 light intensity of 400-800nm full spectrum. 2 The schematic diagram for detecting cell survival rate using cck-8 kit after 8h incubation after 30min irradiation.

[0039] Figure 11 The schematic diagram for co-localization confocal fluorescence imaging after 30min incubation of c-BBP and t-BBP with P02 cells, and then 30min incubation with Mitotracker (mitochondrial dye). DETAILED DESCRIPTION

[0040] Example 1 Synthesis of complex

[0041] In this example, BODIPY-based platinum drug complexes c-BBP and t-BBP were prepared, and the molecular formula was C 36 H 42 B2F4N8Pt, and the chemical structural formula was:

[0042] .

[0043] The above BODIPY-based platinum drug complexes were prepared by the following steps:

[0044] Under nitrogen protection, add trifluoroacetic acid drop by drop to a dichloromethane solution (150 ml) containing 2, 4-dimethylpyrrole (2.0 g, 21 mmol) and 4-aldehyde pyridine (1.2 g, 10 mmol), stir at room temperature for 24 h, track the reaction by TLC, after the reaction is completed, continue to add a THF solution containing DDQ (13 mmol, 2.5 g) drop by drop to the reaction liquid 50 mL, continue to stir for 30 minutes, then add 5 mL of triethylamine and 5 mL of boron trifluoride ether drop by drop to the reaction liquid, continue to stir at 0°C overnight. After the reaction is completed, add water 100 mL, dichloromethane 100 x 2 mL to the reaction liquid in turn, dry the organic phase with anhydrous sodium sulfate, remove the solvent under reduced pressure, separate by column chromatography to obtain a dark red solid 0.7 g, which is 4-pyridine BODIPY.

[0045] The product 4-pyridine BODIPY was characterized by nuclear magnetic resonance, and the specific nuclear magnetic resonance characterization was Yield: 20%. 1 H NMR (CDCl3, ppm): δ 8.72-8.70 (d, 2H, J = 6 Hz), 7.32-7.30 (d, 2H, J = 6 Hz), 6.0 (s, 2H), 2.56 (s, 6H,), 1.48 (s, 6H).

[0046] Respectively, cis-dichlorodiammine platinum, trans-dichlorodiammine platinum and AgNO3 were dissolved in DMF, reacted at 50°C for 24 h, the solution was centrifuged, the supernatant was added to 4-pyridine BODIPY, and the reaction was continued at 50°C for 24 h, the reaction liquid was added to ether and recrystallized, the precipitate was taken after centrifugation, and then washed with methanol for 2-3 times, and dried to obtain the product c-BBP and t-BBP, respectively.

[0047] As shown in Figure 1 , it is the hydrogen nuclear magnetic resonance spectrum of the products c-BBP and t-BBP. It can be proved that the synthesis of the two complexes is successful and the structure is correct.

[0048] Example 2: Detection of active oxygen ability of the complex

[0049] In this example, c-BBP and t-BBP prepared in Example 1 were detected by DCFH, DHR123, ABDA and HPF fluorescent probes for photodynamic detection of c-BBP and t-BBP, and the yield of each type of active oxygen was calculated. In the photodynamic detection, cell toxicity and cell imaging experiment, the c-BBP and t-BBP sample solution was prepared as 1 mg / ml solution as sample solution, and the solvent was DMSO:H2O=1:9

[0050] 1. DCFH detection

[0051] Firstly, 0.5 ml of 1 mM DCFH-DA ethanol solution was added to 2 ml of 0.01 N NaOH, and stirred at room temperature for 30 min; then the pH value of the solution was adjusted to about 7 by using 10 ml of 25 mM PBS with pH value of 7.4. When testing, 10 μl of c-BBP and t-BBP sample solution (1 mg / ml) was respectively added to 990 μl of prepared DCFH solution, mixed well, and then 100 μl of the mixture was dropped into a 96-well plate, and the fluorescence intensity at 0 s was measured by using an enzyme marker. The whole spectrum light source with 400-800 nm (40 mW / cm 2 ) was used for irradiation, and the value was recorded every 30 s, and the measurement was ended at 5 min. The results are shown in Figure 2 , the fluorescence intensity of c-BBP compared with DCFH solution was enhanced by about 9 times, and the fluorescence intensity of cBBP compared with DCFH solution was enhanced by about 21 times, which proved that the total amount of active oxygen of cBBP was higher than that of c-BBP, and the total amount of active oxygen of the two trans complexes was lower than that of the two cis complexes.

[0052] ABDA detection

[0053] 1 mg of ABDA was dissolved in 97 μl of DMSO to obtain an ABDA DMSO solution. 2 μl of the ABDA DMSO solution was respectively added to 1 ml of c-BBP and t-BBP sample solution, and the ultraviolet absorbance at 200-800 nm at 0 s was measured by using an enzyme marker. Then the whole spectrum light source with 400-800 nm (40 mW / cm 2 ) was used for irradiation, and the value was recorded every 30 s. According to the absorbance reduction at 358 nm, 378 nm and 400 nm, the singlet oxygen yield of the sample was calculated. The results are shown in Figure 3 , taking rose Bengal (RB) as a 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 active oxygen species produced by cBBP was mainly singlet oxygen, and c-BBP belonged to type II photosensitizer, while the active oxygen species produced by c-BBP was more superoxide radical and hydroxyl radical, which belonged to type I photosensitizer.

[0054] DHR123 detection

[0055] In 990 μl of superoxide anion detection reagent dihydro rhodamine 123 (DHR123), 10 μl of c-BBP and t-BBP sample solution was respectively added, and the whole spectrum light source with 400-800 nm (40 mW / cm 2 ) was used for irradiation. The fluorescence intensity was measured by using a fluorescence spectrophotometer, and the value was recorded every 1 min, and the measurement was ended at 5 min. The results are shown in Figure 4As shown, the ability of c-BBP molecules to produce superoxide anion was similar to that of t-BBP molecules, being 15.6 times and 15.7 times that of the blank control group, respectively. The ability of c-BBP molecules and t-BBP molecules to produce superoxide anion was also higher than that of cBBP and tBBP under the same solution conditions.

[0056] HPF detection

[0057] Hydroxyl radical detection reagent hydroxyphenyl fluorescein (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 a 5 μM HPF PBS solution, respectively, and irradiated with a full-spectrum light source of 400-800 nm (40 mW / cm 2 ) and the fluorescence intensity was measured in a fluorescence spectrophotometer, recording values every 1 min, and measuring up to 5 min. The results are shown in Figure 5 As shown, the ability of c-BBP molecules to produce hydroxyl radicals was significantly higher than that of t-BBP molecules, with the ability of c-BBP molecules to produce hydroxyl radicals reaching 15.7 times that of the blank control group, while the ability of t-BBP molecules to produce hydroxyl radicals was only 4.6 times that of the blank control group. Hydroxyl radicals have strong oxidative ability among various active oxygen species, and the high yield of c-BBP molecules proves that they can cause greater damage to tumor cells, and the process of producing hydroxyl radicals is not as dependent on oxygen as other active oxygen species, so it can achieve higher killing effect in the hypoxic microenvironment of tumors. Similarly, the ability of c-BBP molecules to produce hydroxyl radicals is higher than that of cBBP, and the ability of t-BBP molecules to produce hydroxyl radicals is also higher than that of tBBP.

[0058] Example 3 Cell cytotoxicity detection of the complex

[0059] Cytotoxicity detection of the original cisplatin and transplatin

[0060] P02 cells (mouse pancreatic cancer cells) and Hela cells (human cervical cancer cells) were first added to 3 ml of trypsin digestion solution in the cell culture dishes for 4 minutes, and then transferred to centrifuge tubes after digestion was complete. 10 μl was taken to a cell counting plate for counting, and the cells were centrifuged and then added to culture medium to prepare a cell suspension with a cell count of 10 w / ml. 100 μl of P02 cells and Hela cells with a cell count of 10 w / ml were plated in each well of a 96-well plate, and incubated for 24 h. Different concentrations of cisplatin and transplatin were added to the cells and incubated for 24 h, and then cck-8 was added and incubated for 1 h. The absorbance value of each well of the 96-well plate at 450 nm was measured using an enzyme marker, and the survival rate of the cells was detected. In the dark, the IC 50 of cisplatin for P02 cells was 6.3889 μg / mL, and the IC 502.3899 μg / mL, IC of cisplatin on P02 cells under light condition 50 7.7734 μg / mL, IC on Hela cells 50 3.5715 μg / mL, it can be seen that the original cisplatin has no special response to light and dark conditions, while the transplatin has an IC on P02 cells and Hela cells under light condition and dark condition 50 both greater than 100 μg / mL, proving that the killing of tumor cells by transplatin is extremely low.

[0061] 2. Cytotoxicity detection of c-BBP and t-BBP in dark

[0062] 3 ml of trypsin digestive juice was first added to P02 and Hela cell culture dishes respectively, and waited for 4 minutes. After digestion was completed, it was placed in a centrifuge tube, 10 μl was taken to a cell counting plate for counting, and after centrifugal separation, the cell suspension with a cell number of 10 w / ml was prepared by adding culture medium. 100 μl of P02 cells with a cell number of 10 w / ml was plated in each well of a 96-well plate, and incubated for 24 h. After c-BBP and t-BBP sample solutions were added to the cells for co-incubation for 24 h, cck-8 was added for incubation for 1 h, and the absorption value of each well in the 96-well plate at 450 nm was measured by using an enzyme marker to detect the survival rate of cells, and the results are shown in Figs. Figure 6 , 7, under dark conditions, the IC of c-BBP molecules on P02 cells 50 was 54.4093 μg / mL, and the IC on Hela cells 50 was 19.1763 μg / mL, which had a killing effect on tumors; while the IC of t-BBP molecules on the two kinds of cells 50 were both greater than 100 μg / mL, similar to transplatin, which had an extremely low killing effect on tumors.

[0063] 3. Cytotoxicity detection of c-BBP and t-BBP under light

[0064] P02 and Hela cell 96-well plates were plated respectively, and incubated for 24 h. After c-BBP and t-BBP sample solutions were added to the cells for co-incubation for 4 h, the whole spectrum light intensity of 40 mW / cm 2 was irradiated for 15 min, and then incubated for 8 h. After cck-8 was added for incubation for 1 h, the absorption value of each well in the 96-well plate at 450 nm was measured by using an enzyme marker to detect the survival rate of cells, and the results are shown in Figs. Figure 8 , 9, under light conditions, the IC of c-BBP molecules on P02 cells 50 was 0.7623 μg / mL, and the IC on Hela cells 50was 0.6361 μg / mL, indicating that c-BBP has a strong killing effect on tumors under light conditions, which shows that the killing effect of c-BBP molecules on tumors can be greatly enhanced by light, and the lower toxicity in the dark condition can ensure biological safety, while the IC 50 of t-BBP molecules on the two cells is greater than 50 μg / mL, and the tumor killing is still low.

[0065] 4. Comparison of the phototoxicity of c-BBP and cBBP

[0066] A 96-well plate with P02 cells was prepared and incubated for 24 h, and then c-BBP and cBBP sample solutions of the same concentration were added. After the cells were incubated for 8 h, they were irradiated with a full-spectrum light intensity of 40 mW / cm 2 for 30 min, and then incubated for another 8 h. Then cck-8 was added and incubated for 1 h. The survival rate of the cells was detected by measuring the absorbance value of each well of the 96-well plate at 450 nm using an enzyme marker. The results are shown in Figure 10 , and the cytotoxicity of c-BBP molecules is significantly higher than that of the previous cBBP molecules, indicating that c-BBP molecules have a higher anti-tumor effect.

[0067] Example 4. Complex cell co-localization detection

[0068] In a confocal dish, 2 ml of P02 cells with a cell count of 10 w / ml were added and incubated in an incubator for 24 h. c-BBP and t-BBP sample solutions were added and incubated for 30 min, and then washed with PBS. Then MitoTracker (mitochondrial fluorescent probe) was added and incubated for another 30 min. After washing with PBS, 2 ml of PBS was added. Co-localization was performed on a confocal microscope. The results are shown in Figure 11 , MitoTrack mitochondrial dye can locate the mitochondria of cells and show red fluorescence, while the fluorescence of c-BBP and t-BBP molecules is green. When the two are observed at the same time, 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 molecules, while t-BBP cannot locate the mitochondria, with a PCC of 0.4.

Claims

1. A BODIPY-based photosensitizer-complexed platinum complex, characterized in that, cisplatin complex c-BBP or transplatin complex t-BBP, the molecular formula of the cisplatin complex c-BBP and the transplatin complex t-BBP being C 36 H 42 B2F4N 10 O6Pt, respectively, and the structure formula of the cisplatin complex c-BBP and the transplatin complex t-BBP being as follows: 。 2. A method of preparing the BODIPY-based photosensitizer complexed platinum complex of claim 1, characterized by, The reaction process comprises the following steps: 。 3. The method of claim 2, wherein, The specific preparation steps are as follows: Step 1) 2, 4-dimethylpyrrole and 4-aldehyde pyridine are dissolved in dichloromethane solution under nitrogen protection, and stirred at room temperature for 24 h under the catalysis of trifluoroacetic acid. The reaction is tracked by TLC. After the reaction is completed, DDQ THF solution is continuously added to the reaction liquid under ice bath condition, and stirred for 30-40 min. Then, triethylamine and boron trifluoride ether complex are sequentially added to the reaction liquid, and the stirring is continued at 0 ℃ for 10-12 h. After the reaction is completed, the reaction liquid is quenched with pure water, and then extracted and washed with dichloromethane. The collected organic phase is dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation under reduced pressure. After separation by column chromatography, 4-pyridine BODIPY in dark red solid is obtained. Step 2) cis-dichlorodiammine platinum or trans-dichlorodiammine platinum is respectively dissolved in DMF with AgNO3, and reacted at 50-60 ℃ for 24-30 h. The solution is centrifuged, and the supernatant is taken and added to 4-pyridine BODIPY prepared in step 1). The reaction is continued at 50-60 ℃ for 24-30 h. The reaction liquid is recrystallized in ether, and the precipitate is taken after centrifugation. The precipitate is washed with methanol for 2-3 times, and dried to obtain the products c-BBP and t-BBP, respectively. The anion is nitrate ion, and the platinum is divalent.

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

5. The preparation method according to claim 3, characterized in that, In step 2) for preparing cis-platinum complex c-BBP, cis-dichlorodiammine platinum is dissolved in DMF with AgNO3, and reacted at 50-60 ℃ for 24-30 h. The solution is centrifuged, and the supernatant is taken and added to 4-pyridine BODIPY prepared in step 1). The reaction is continued at 50-60 ℃ for 24-30 h. The reaction liquid is recrystallized in ether, and the precipitate is taken after centrifugation. The precipitate is washed with methanol for 2-3 times, and dried to obtain the product c-BBP. The anion is nitrate ion, and the platinum is divalent.

6. The preparation method according to claim 3, characterized in that, In step 2) for preparing trans-platinum complex c-BBP, 7. The production method according to claim 5 or 6, characterized by, trans-dichlorodiammine platinum is dissolved in DMF with AgNO3, and reacted at 50-60 ℃ for 24-30 h. The solution is centrifuged, and the supernatant is taken and added to 4-pyridine BODIPY prepared in step 1). The reaction is continued at 50-60 ℃ for 24-30 h. The reaction liquid is recrystallized in ether, and the precipitate is taken after centrifugation. The precipitate is washed with methanol for 2-3 times, and dried to obtain the product t-BBP. The anion is nitrate ion, and the platinum is divalent. The molar amount of cis-dichlorodiammine platinum, AgNO3 and 4-pyridine BODIPY is 1:2:

2. The molar amount of trans-dichlorodiammine platinum, AgNO3 and 4-pyridine BODIPY is 1:2:

2.

8. Use of a BODIPY-based photosensitizer complexed platinum complex according to claim 1 for the manufacture of a medicament for inhibiting cancer cells.

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