Sulfhydrylated platinum nano-particles as well as preparation method and application thereof

Abstract

The invention relates to a sulfhydrylated platinum nanoparticle, the surface of a metal platinum nanoparticle is modified and grafted with a sulfydryl polymer, and free sulfydryl on the surface of the sulfhydrylated platinum nanoparticle helps the nanoparticle to stay at a tumor site for a long time, so that the nanoparticle is convenient to cooperate with sensitization radiotherapy in a radiotherapy period, and the sensitization effect of the metal platinum in the tumor radiotherapy process is maximized; and the preparation method of the platinum thiolate nanoparticles is simple, and the platinum thiolate nanoparticles have obvious effects of retention in tumors and tumor radiotherapy sensitization, and have good application prospects.

Description

Technical Field

[0001] The present invention relates to the field of tumor treatment, and in particular to a thiolated platinum nanoparticle and a preparation method and application thereof. Background Art

[0002] The application and mechanism of platinum nanoparticles in tumor radiosensitization have received extensive attention in recent years. Platinum nanoparticles can enhance the sensitivity of tumor cells to radiation. Studies have shown that platinum nanoparticles can effectively absorb radiation energy and convert it into heat energy or electrons, thereby increasing the generation of free radicals and reactive oxygen species (ROS) in tumor cells. These reactive oxygen species can damage the DNA of tumor cells, leading to cell apoptosis or necrosis, thereby enhancing the killing effect of radiotherapy. In addition, platinum nanoparticles can further promote the sensitivity of tumor cells to radiation by affecting the redox balance in cells. In addition, platinum nanoparticles can sensitize radiotherapy by changing the tumor microenvironment. Hypoxia and immunosuppression in the tumor microenvironment are important factors leading to poor radiotherapy effects. Platinum nanoparticles can catalyze the decomposition of water molecules to produce oxygen, thereby alleviating the hypoxic state of the tumor microenvironment and improving the effect of radiotherapy. At the same time, platinum nanoparticles can also enhance the body's anti-tumor immune response by regulating the function of immune cells, further improving the efficacy of radiotherapy. In the prior art, the water solubility, dispersibility, biocompatibility and other properties of platinum nanoparticles can be improved by polymer modification (such as patent US20220079983A1), thereby increasing the application potential of platinum nanoparticles. Among them, the size effect of nanoparticles is mainly used to enhance the enrichment of nanoparticles at the tumor site to enhance radiotherapy sensitivity. However, metal platinum nanoparticles still cannot stay at the tumor site for a long time. It is expected that in actual application, metal platinum nanoparticles need to be injected repeatedly. This treatment method will not only cause pain to patients, but also cause safety risks due to the cumulative dose of metal platinum in the body and uncontrollable metabolism in the body. Therefore, it is necessary to provide a new strategy to increase the feasibility of metal platinum nanoparticles in the clinical application of tumor radiotherapy sensitization. Summary of the invention

[0003] In order to solve the above problems, the present application provides a thiolated platinum nanoparticle. The surface of the platinum nanoparticle contains a large number of free thiol groups. By combining with the thiol groups on various protein molecules in biological tissues to form disulfide bonds, the platinum nanoparticles are fixed to the tumor site, combined with external radiotherapy for the tumor, to safely and effectively inhibit tumor growth.

[0004] The first object of the present invention is to provide a thiolated platinum nanoparticle for preparing a radiotherapy sensitizing preparation, characterized in that the thiolated platinum nanoparticle comprises a platinum nanoparticle core and a free thiol group, the free thiol group is connected to the platinum nanoparticle core through a polymer, and the polymer is selected from chitosan or branched PEG.

[0005] Furthermore, the thiolated platinum nanoparticles include a chitosan outer layer containing a plurality of free thiol groups and a platinum nanoparticle inner core.

[0006] Furthermore, the chitosan containing multiple free thiol groups is obtained by modifying the surface amino groups of chitosan with cysteine, or the chitosan containing multiple free thiol groups is commercially available thiolated chitosan.

[0007] Furthermore, the thiolated platinum nanoparticles are obtained by modifying the surface of metal platinum nanoparticles with a polymer, the chain end of the polymer contains at least two thiol groups, and the polymer is selected from any one or two of chitosan and PEG. The polymer has at least one thiol group at the chain end that is combined with the platinum metal nanoparticle, and at least one thiol group at the chain end is exposed on the outer layer of the thiolated platinum nanoparticle.

[0008] Furthermore, the average particle size of the thiolated platinum nanoparticles is 7-85 nm.

[0009] Furthermore, the average particle size of the thiolated platinum nanoparticles is 45-85 nm.

[0010] Furthermore, the PEG has a branched structure.

[0011] Furthermore, the free amino groups on the chitosan are modified with cysteine, and the average degree of cysteine ​​modification is 2-8%.

[0012] Furthermore, the thiolated platinum nanoparticles are obtained by connecting the thiolated branched PEG shown in Formula I to the platinum nanoparticle core: Formula Ⅰ.

[0013] Furthermore, the thiolated platinum nanoparticles are prepared by the following steps: S1: Mix equal volumes of an aqueous solution of chloroplatinic acid hexahydrate and an aqueous solution of polyvinyl pyrrolidone, and stir for 30 min in a nitrogen atmosphere in a dark environment to obtain a solution a, wherein the average molecular weight of the polyvinyl pyrrolidone is 4000; S2: adding sodium borohydride solution dropwise into solution a at a dropping speed of 20-100 μL / min, and continuing stirring for 10-15 min to obtain a crude product solution b of platinum nanoparticles; S3: Select an ultrafiltration centrifuge tube with a molecular weight cutoff of 100 kDa, and centrifuge at 4000 rpm for 10 min to obtain platinum nanoparticle solution c after centrifuging solution b; S4: mixing the solution c with an aqueous solution of chitosan or thiolated branched PEG containing multiple free thiols, stirring at 4° C. for 12 to 16 hours to obtain a solution d, wherein the solution d contains the thiolated platinum nanoparticles.

[0014] Furthermore, the concentration of the aqueous solution of chloroplatinic acid hexahydrate and the aqueous solution of polyvinyl pyrrolidone in step S1 is 4 mg / mL.

[0015] Furthermore, the concentration of the sodium borohydride solution in step S2 is 30 mg / mL.

[0016] Furthermore, the mass of the polymer in step S4 is 100 to 300 times the mass of the platinum nanoparticles in solution c.

[0017] Furthermore, the thiolated platinum nanoparticles according to claim 1 are characterized in that they also include step S5: ultrafiltration and concentration of the solution e, using an ultrafiltration centrifuge tube with a molecular weight cutoff of 100 kDa, and centrifuging at 4000 rpm for 10 min.

[0018] The second object of the present invention is to provide an application of thiolated platinum nanoparticles in the preparation of tumor radiotherapy sensitization preparations.

[0019] The present invention has the following beneficial effects: The thiolated platinum nanoparticles of the present invention have good biocompatibility, and a large number of thiol groups are exposed on the surface of the thiolated platinum nanoparticles. The thiol groups bind to proteins on the surface of tumor tissues or cells, thereby helping metal platinum to stay in the tumor site for a long time, which is convenient for coordinating with external radiation therapy cycles to achieve radiotherapy sensitization. The branched chain structure of the polymer is conducive to the distribution of free thiol groups on the surface of platinum nanoparticles, and further realizes the binding effect of free thiol groups with tumor tissues. Therefore, the thiolated platinum nanoparticles of the present invention reduce the irradiation dose while the cumulative dose of platinum nanoparticles used is lower, which greatly reduces the safety risk and has a wide range of application prospects. In addition, the thiolated platinum nanoparticles of the present invention have good dispersibility, are easy to prepare and purify, have the potential for mass production, and are helpful for future market launch. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 is a statistical graph of the platinum content retained in the tumor sites of the two groups of mice in Example B1; Figure 2 is a statistical diagram of the relative content of platinum retained in the tumor sites of the two groups of mice in Example B1 and the administered dose; Figure 3 is a statistical diagram of the absolute content of platinum in different organs of each group of mice in Example B2; Figure 4 is a statistical graph of the platinum content per gram of different organ tissues of each group of mice in Example B2; Figure 5 is a statistical chart showing the percentage of platinum content in different organs of mice in each group in Example B2 to the total dose; Figure 6is a statistical graph showing the percentage of the content of platinum per gram of different organ tissues of each group of mice in Example B2 to the total administered dose; Figure 7 is a statistical graph of platinum concentration in peripheral blood of mice in Example B3; Figure 8 is a statistical diagram of the relative content of platinum in the peripheral blood of mice in Example B3; Fig. 9 It is a statistical graph of the average weight changes of mice in each group in Example B4. DETAILED DESCRIPTION

[0021] In order to further illustrate the technical means and effects adopted by the present invention to achieve the predetermined purpose, the specific implementation methods, methods, steps, structures, characteristics and effects of the amphiphilic drug carrier proposed in the present invention are described in detail below in combination with the accompanying drawings and preferred embodiments.

[0022] The above and other technical contents, features and effects of the present invention will be clearly presented in the following detailed description of the preferred embodiments with reference to the drawings. Through the description of the specific implementation methods, the technical means and effects adopted by the present invention to achieve the predetermined purpose can be more deeply and specifically understood. However, the drawings are only for reference and explanation purposes and are not used to limit the present invention.

[0023] Experimental materials and instruments: Inductively coupled plasma mass spectrometer ICP-MS: Jena M90, Germany Nanoparticle size and zeta potential analyzer: NANO ZS90 Embodiment A1: Preparation of platinum nanoparticles and thiolated platinum nanoparticles, the polymer is PEG: 1. Use pure water as solvent to prepare 4 mg / mL chloroplatinic acid hexahydrate solution and 4 mg / mL polyvinyl pyrrolidone (average molecular weight is about 4000) solution; 2. Take 2 mL of the prepared chloroplatinic acid hexahydrate solution and mix it with an equal volume of polyvinyl pyrrolidone solution, and stir for 30 min under the condition of avoiding light and passing nitrogen; 3. Add 200 μL of sodium borohydride solution (30 mg / mL) to the nitrogen-filled chloroplatinic acid hexahydrate-polyvinyl pyrrolidone mixed solution at a rate of 20-100 μL / min while stirring on a stirring table (1500 rpm) at room temperature. After all the addition is completed, react for 10-15 minutes to obtain a crude product solution of platinum nanoparticles; 4. The collected platinum nanoparticle solution after filtration was concentrated by ultrafiltration. An ultrafiltration centrifuge tube with a molecular weight cutoff of 100 kDa was selected and the centrifugation parameters were 4000 rpm for 10 min. After centrifugation, a platinum nanoparticle dispersion was obtained. Testing showed that the particle size distribution of the obtained platinum nanoparticles was about 20~50 nm, and the above synthesis method was reproducible.

[0024] 5. Add 4-Arm-PEG-SH to the platinum nanoparticle dispersion obtained in step 4, wherein the mass of 4-Arm-PEG-SH is about 250 times the mass of the platinum nanoparticles, mix well, place at 4°C ambient temperature, and stir overnight. The product is filtered through a dextran G25 gel column to remove unconnected 4-Arm-PEG-SH, collect the product, and obtain the thiolated platinum nanoparticles. The structure of the obtained thiolated platinum nanoparticles is: platinum nanoparticles as the core, part of the thiol groups on 4-Arm-PEG-SH are coupled with platinum nanoparticles to form a thiolated polymer outer layer, and the whole forms a core-shell structure. Due to the rigid characteristics of the 4-Arm-PEG-SH branched structure, in addition to a small amount of thiol groups connected to the core of the platinum nanoparticles, there are still a large number of free thiol groups retained in the outer layer of the thiolated platinum nanoparticles, which are used to form biological adhesion between the tumor site and the tissue, and prolong the retention time of the platinum nanoparticles at the tumor site.

[0025] The particle size was detected by nanoparticle size and zeta potential instrument, and the particle size of thiolated platinum nanoparticles was about 45~50 nm.

[0026] Embodiment A2: Preparation of thiolated platinum nanoparticles, the polymer is chitosan: Repeat steps 1 to 4 of Example A1 to prepare a platinum nanoparticle dispersion; Preparation of thiolated chitosan: 1. Weigh 15.00 mg chitosan hydrochloride, dissolve in 3 mL pure water, add 0.5 M sodium bicarbonate solution and adjust the pH to 5.95-6.05; 2. Weigh 5.65 mg of cysteine, 13.4 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and 8.04 mg of N-hydroxysuccinimide and dissolve them in 2 mL of anhydrous dimethyl sulfoxide that has been deoxygenated with nitrogen in advance. Activate at room temperature in the dark for 1 hour. After activation, add all the activation solution to the pH-adjusted chitosan hydrochloride solution on a heated stirring table and react in the dark for 5 hours. 3. Add 14.33 mg TCEP to the mixed solution after the reaction and react for 0.5 h. After the reaction, add 0.5 M hydrochloric acid until the pH is 0.89. Put all the liquid into a dialysis bag with a molecular weight cutoff of 10,000 Da and dialyze in hydrochloric acid at pH 4 for 36 h. After the dialysis, freeze the solution in the bag at -80 ° C and freeze-dry (cold trap temperature -80 ° C, pressure less than 1.45 mbar) to obtain thiol chitosan.

[0027] The prepared thiolated chitosan modified platinum nanoparticles, specifically: use pure water to prepare 2 mg / mL thiolated chitosan solution, use pure water to dilute to obtain 2 mg / mL platinum nanoparticle solution, take 50 μL of each solution, mix and let stand for 0.5h, and then obtain chitosan modified thiolated platinum nanoparticles. Also try three feed ratios: 2 mg / mL thiolated chitosan solution + 1 mg / mL platinum nanoparticle solution, 1 mg / mL thiolated chitosan solution + 1 mg / mL platinum nanoparticle solution, and 1 mg / mL thiolated chitosan solution + 2 mg / mL platinum nanoparticle solution.

[0028] The particle size of the thiolated platinum nanoparticles prepared with different feed ratios was detected by using a nanoparticle size and zeta potential instrument. The results showed that the particle size of the thiolated platinum nanoparticles prepared by 2 mg / mL thiolated chitosan solution + 2 mg / mL platinum nanoparticle solution was about 60-85 nm. The particle size of the thiolated platinum nanoparticles prepared by 2 mg / mL thiolated chitosan solution + 1 mg / mL platinum nanoparticle solution was about 17-62 nm; the particle size of the thiolated platinum nanoparticles prepared by 1 mg / mL thiolated chitosan solution + 2 mg / mL platinum nanoparticle solution was about 7-28 nm.

[0029] Example A3: Determination of the Surface Thiol Content of Thiolated Platinum Nanoparticles The free thiol content exposed by the thiolated platinum nanoparticles prepared in Example A1 was detected using the Biyuntian free thiol detection kit (DTNB method). According to the instructions of the kit, the absorbance of the sample and the standard in the well plate at 412 nanometers was detected using an ELISA instrument, and the content of the thiol in the sample was calculated by substituting the curve determined by the standard. The results showed that no free thiol was detected in the unmodified platinum nanoparticle sample, and the free thiol content of the thiolated platinum nanoparticle sample modified with 4-Arm-PEG-SH was about 19.29 μM when the sample concentration was 0.2 mg / mL. It shows that free thiol groups do exist on the surface of the thiolated platinum nanoparticles of the present invention, which supports that the thiolated platinum nanoparticles of the present invention form disulfide bonds in biological tissues to enhance the retention effect at the tumor site, thereby enhancing long-term sensitization radiotherapy and improving the efficacy.

[0030] Example B1: Total Retention and Relative Content of Thiolated Platinum Nanoparticles at Tumor Sites A mouse subcutaneous tumor model was established and the mice were randomly divided into 2 groups: Pt NP: 50 μL platinum nanoparticles injected intratumorally; Pt / CS-SH NP: 50 μL of thiolated platinum nanoparticles were injected intratumorally, and the polymer was chitosan.

[0031] The platinum content in the two groups of injected samples was equal. 72 hours after injection, the mice were euthanized, and the tumor tissue samples were dissected and dissolved with aqua regia. After complete digestion, a platinum-containing solution was obtained. The platinum content in the tumor tissue of each mouse was detected by ICP-MS. Figure 1 is a statistical graph of the platinum content retained in the tumor sites of the two groups of mice in Example B1, Figure 2 It is a statistical diagram of the relative content of platinum retained in the tumor site of two groups of mice in Example B1 and the dosage. The results show that the amount of platinum retained in the mouse tumor site in Pt / CS-SH NP is significantly higher than that in Pt NP. The retention of platinum in Pt / CS-SH NP can reach 40% 72 hours after injection, far exceeding the 10% of Pt NP, indicating that the thiolated platinum nanoparticles of the present invention are relatively stable in a physiological environment and can significantly prolong the retention time in the tumor site, thus having the potential for further application in radiotherapy sensitization. At the same time, the inventors used the same experimental method and testing means to detect the retention of chitosan-modified platinum nanoparticles (Pt / CS NP) without free thiol groups in tumor tissues. The results showed that 72 hours after the in situ injection of Pt / CS NP, only about 18% of the total amount of platinum was retained in the tumor site, which was completely inferior to the thiolated platinum nanoparticles. Just like the purpose of using polymers to modify metal nanoparticles in the vast majority, Pt / CS NP does not contain free thiol groups. The presence of polymers can help the biocompatibility of nanoparticles in the blood circulation after intravenous injection, increase bioavailability, and use the EPR effect to reach the tumor site as much as possible, but it cannot guarantee the long-term retention of nanoparticles that reach the tumor site. The thiolated platinum nanoparticles of the present invention can achieve a large amount of long-term enrichment of platinum metal in the tumor site by in situ injection of the tumor, which can better achieve radiosensitization. It should be noted that, unlike implanted large-sized platinum single substance products, the thiolated platinum nanoparticles of the present invention also achieve metal metabolism at the same time, improving the safety and practicality of platinum nanoparticles in tumor radiosensitization.

[0032] Example B2: Biodistribution of thiolated platinum nanoparticles A subcutaneous tumor model of mice was established according to the method of Example B1, and the mice were randomly divided into two groups. Thiolated platinum nanoparticles or platinum nanoparticles were injected intratumorally in a volume of 50 μL. The concentration of platinum in the two injection samples was the same.

[0033] 72 hours after injection, the mice were euthanized, and the main organs (heart, liver, spleen, lung, and kidney) were dissected and the weight of each organ was recorded. Then, the organ tissue samples were digested with aqua regia, and the platinum content was detected by ICP-MS. Figure 3 is a statistical diagram of the absolute content of platinum in different organs of each group of mice in Example B2; Figure 4 is a statistical graph of the platinum content per gram of different organ tissues of each group of mice in Example B2; Figure 5 is a statistical chart showing the percentage of platinum content in different organs of mice in each group in Example B2 to the total dose; Figure 6 The figure is a statistical chart of the percentage of the total dosage of platinum in each gram of different organ tissues of each group of mice in Example B2. The results show that the distribution of thiolated platinum nanoparticles in the main organs of mice is significantly lower than that of Pt NP, which verifies that the thiolated platinum nanoparticles in Example B1 are more concentrated in the tumor site, indicating that the potential safety risk of thiolated platinum nanoparticles to the main organs is lower.

[0034] Example B3: Pharmacokinetic Study of Thiolated Platinum Nanoparticles (Absolute Concentration and Metabolism Percentage) Modeling and administration were performed according to the method of Example B1, and peripheral blood samples of mice were collected at 2, 4, 8, 12, 24, and 72 hours after intratumoral injection, and the platinum content in the blood samples was detected by ICP-MS. Figure 7 is a statistical graph of platinum concentration in peripheral blood of mice in Example B3, Figure 8 It is a statistical graph of the relative content of platinum in the peripheral blood of mice in Example B3. The results show that the increase and decrease trend of the platinum content in the peripheral blood of mice is consistent with the general law of pharmacokinetics. After intratumoral injection of thiolated platinum nanoparticles, the total amount entering the blood is significantly lower than that of unmodified platinum nanoparticles. The thiolation modification significantly prolongs the retention time of platinum nanoparticles in the tumor site and reduces the metabolic rate.

[0035] Example B4: Verification of the sensitization effect of external radiotherapy The mouse back subcutaneous tumor model was established. Specifically, CT26 cells were inoculated subcutaneously on the back of Balb / c mice, with approximately 1×10 6 cells, and when the tumor volume reaches 100 mm 3 The tumor-bearing mice were randomly divided into five groups: Normal saline group: 50 μL normal saline was injected intratumorally; Pt / CS-SH group: 50 μL, 2 mg / mLqthiolated platinum nanoparticles were injected intratumorally; Normal saline + irradiation group: after intratumoral injection of 50 μL normal saline, three radiation treatments were performed; Pt+ irradiation group: 50 μL, 2 mg / mL platinum nanoparticles were injected intratumorally, followed by 3 radiotherapy sessions; Pt-CS+irradiation group: After intratumoral injection of 50 μL, 2 mg / mL chitosan-modified platinum nanoparticles, three radiotherapy sessions were performed. The preparation method of chitosan-modified platinum nanoparticles was similar to that of thiolated platinum nanoparticles, except that chitosan was not modified with cysteine ​​and did not contain free thiol groups. Pt / CS-SH+ irradiation group: After intratumoral injection of 50 μL, 2 mg / mL thiolated platinum nanoparticles, three radiotherapy sessions were performed. The irradiation operation was that the tumor site of the mice received local external radiation therapy with a dose of 2 Gy on the 1st, 3rd, and 5th day after injection of different samples.

[0036] The tumor volume of mice was recorded every two days, and the tumor inhibition rate was calculated (tumor inhibition rate = (1-(tumor volume of treatment group-initial tumor volume of treatment group) / (tumor volume of normal saline group-initial tumor volume of normal saline group))*100%). The average tumor inhibition rate calculation results on the 9th, 14th, and 18th days after treatment are shown in the following table: Further analysis of the tumor inhibition rate data showed that the introduction of Pt, Pt-CS, and Pt / CS-SH had an effect on the radiotherapy effect compared with radiotherapy alone (normal saline + irradiation group). The difference in tumor inhibition rate between the groups on day 18 was calculated. The difference in tumor inhibition rate between the Pt / CS-SH+irradiation group and the normal saline + irradiation group was 31.61%; and the difference in tumor inhibition rate between the Pt+irradiation group and radiotherapy alone was 3.93%; the difference in tumor inhibition rate between Pt / CS-SH combined with radiotherapy and radiotherapy alone was about 8 times the difference in tumor inhibition rate between Pt combined with radiotherapy and radiotherapy alone, proving that the effect of the thiolated platinum nanoparticles in enhancing radiotherapy is more significant.

[0037] Fig. 9 It is a statistical graph of the average weight change of mice in each group in Example B4. Combined with the results of the tumor inhibition rate and the weight curve, it shows that the thiolated platinum nanoparticles combined with radiotherapy described in the present invention have a significant inhibitory effect on tumor growth. The free thiol groups on the surface of the thiolated platinum nanoparticles help the retention of platinum metal at the tumor site, and play a sensitizing effect in multiple radiotherapy sessions, thereby significantly improving the radiotherapy efficacy, and does not cause a significant change in the weight of mice, indicating that the thiolated platinum nanoparticles described in the present invention are less toxic to mice and have a higher safety.

[0038] This example, combined with the data of Example B1 to Example B3, illustrates that the retention effect of thiolated platinum nanoparticles at the tumor site improves the utilization of platinum metal in radiosensitization, which is of great significance in reducing the frequency and dosage of administration, and further reduces the potential safety risks of metals to organisms.

[0039] Obviously, those skilled in the art can make various changes and modifications to the invention without departing from the spirit and scope of the invention. Thus, if these modifications and variations of the invention fall within the scope of the claims of the invention and their equivalents, the invention is also intended to include these modifications and variations.

Claims

1. A platinum thiolate nanoparticle for preparing a radiotherapy sensitization preparation, characterized in that: The thiolated platinum nanoparticles include a platinum nanoparticle core and free thiol groups, wherein the free thiol groups are connected to the platinum nanoparticle core via a polymer, and the polymer is selected from one or both of chitosan or branched PEG modified with no less than two thiol groups on a single molecule.

2. The thiolated platinum nanoparticles according to claim 1, characterized in that: The thiolated platinum nanoparticles include a chitosan outer layer containing a plurality of free thiol groups and a platinum nanoparticle inner core.

3. The thiolated platinum nanoparticles according to claim 2, characterized in that: The chitosan containing multiple free thiol groups is obtained by modifying the surface amino groups of chitosan with cysteine; or the chitosan containing multiple free thiol groups is commercially available thiolated chitosan.

4. The thiolated platinum nanoparticles according to claim 1, characterized in that: The thiolated platinum nanoparticles are obtained by connecting the thiolated branched PEG shown in Formula I to the platinum nanoparticle core: Formula Ⅰ.

5. The thiolated platinum nanoparticles according to claim 1, characterized in that The average particle size of the mercapto platinum nanoparticles is 7nm-85nm.

6. The thiolated platinum nanoparticles according to claim 3, characterized in that: The modification degree of cysteine ​​on chitosan is 2% to 8% on average.

7. A method for preparing the thiolated platinum nanoparticles according to claim 1, characterized in that: The thiolated platinum nanoparticles are prepared by the following steps: S1: Mix equal volumes of an aqueous solution of chloroplatinic acid hexahydrate and an aqueous solution of polyvinyl pyrrolidone, and stir for 30 min in a nitrogen atmosphere in a dark environment to obtain a solution a, wherein the average molecular weight of the polyvinyl pyrrolidone is 4000; S2: adding sodium borohydride solution dropwise into solution a at a dropping speed of 20-100 μL / min, and continuing stirring for 10-15 min to obtain a crude product solution b of platinum nanoparticles; S3: Select an ultrafiltration centrifuge tube with a molecular weight cutoff of 100 kDa, centrifuge and wash solution b to obtain platinum nanoparticle solution c; S4: Mix the solution c with an aqueous solution of chitosan containing multiple free thiol groups or thiol-modified branched PEG of formula I, and stir at 4° C. for 12 to 16 hours to obtain a solution d.

8. The preparation method according to claim 5, characterized in that: The concentration of the aqueous solution of chloroplatinic acid hexahydrate and the aqueous solution of polyvinyl pyrrolidone in step S1 is 4 mg / mL.

9. The preparation method according to claim 5, characterized in that: The concentration of the sodium borohydride solution in step S2 is 30 mg / mL.

10. The preparation method according to claim 5, characterized in that: The mass of the polymer in step S4 is 100 to 300 times the mass of the platinum nanoparticles in solution c.

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