Preparation method and application of tumor-targeted photo-thermal / radiotherapy sensitizer

Abstract

The invention discloses a preparation method and application of a tumor-targeted photo-thermal / radiotherapy sensitizer, and belongs to the technical field of biomedical materials. The preparation method comprises the following steps: (1) preparing Fe3O4 (at) C nanoparticles; (2) dispersing the Fe3O4 (at) C nano-particles in a solution, adding platinum acetylacetonate, and depositing Pt nano-particles through thermal degradation in a protective gas atmosphere to prepare Fe3O4 (at) C (at) Pt nano-particles; and (3) combining the nano-iron platinum particles with a tumor targeting ligand in an electrostatic adsorption manner to prepare the tumor targeting nano-iron platinum particles. Compared with a traditional iron-based nano material, the prepared nano iron-platinum particles have better POD enzyme activity and CAT enzyme activity, and the Fenton catalytic capacity and the photo-thermal conversion capacity of the nano iron-platinum particles are higher. In addition, the hydrogel has good biocompatibility. The compound has no significant toxicity to normal cells, has the potential of targeting tumor sites, and has selective killing ability to tumor cells.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical materials, and particularly relates to a preparation method and application of a tumor-targeted photothermal / radiotherapy sensitizer. Background Art

[0002] At present, anti-tumor treatment methods are mainly divided into two categories: traditional treatment methods and new treatment methods. Traditional treatment methods mainly include surgery, radiotherapy, and chemotherapy. These methods have a wide range of applications, but the curative effect is not good and the side effects are large, seriously affecting the quality of life of patients after recovery. In recent years, new treatment methods that have emerged in the public eye mainly include chemodynamic therapy (CDT), photothermal dynamic therapy (PDT), photothermal therapy (PTT), and immunotherapy.

[0003] Chemodynamic therapy is an anti-tumor treatment method based on the Fenton reaction or Fenton-like reaction to inhibit the growth of tumor cells. Its treatment principle is closely combined with the characteristics of the tumor microenvironment (TME), and the treatment effect is affected by the content of H2O2 in the tumor. Photothermal therapy is a tumor phototherapy method. It stimulates the near-infrared light to be enriched on the photothermal conversion agent entering the tumor tissue, converts the energy of the near-infrared light into heat energy, raises the temperature of the tumor site to 40-45 °C, blocks the nutrient supply of the tumor site, and thus induces apoptosis or necrosis of tumor cells. Through the precise irradiation of the tumor site with near-infrared light, the damage to normal tissues can be reduced and surgery is not required, with small trauma and good prognosis for patients. However, the penetration of near-infrared light is insufficient, making it difficult to treat deep tumors, thus greatly affecting the effect of photothermal therapy.

[0004] Tumors are soft tissues with low radiation absorption and deposition capabilities, resulting in insufficient generation of ROS during treatment and poor treatment effects. Therefore, in clinical practice, high doses of radiation are often used to ensure the treatment effect, resulting in serious side effects. More importantly, the application of high radiation doses will exacerbate the degree of tumor hypoxia, and hypoxia will inhibit the further damage of tumor DNA by X-rays, leading to radioresistance. Therefore, by synthesizing nanomaterials that can relieve the hypoxia in tumors, such as catalase (CAT) nanocarriers, perfluorocarbon (PFC) nanoemulsions, and artificial red blood cells, it is expected to achieve anti-tumor effects while reducing high radiation doses.

[0005] Nanodrugs have achieved active regulation of the tumor microenvironment through innovative design, especially showing unique advantages in relieving hypoxia and enhancing oxygen-related therapies. The combination of photothermal therapy and radiotherapy with nanomaterials with hypoxia regulation has formed a new paradigm for precise tumor treatment. With the continuous progress of nanotechnology and the in-depth development of translational research, such strategies are expected to bring breakthrough progress to clinical tumor treatment. Summary of the Invention

[0006] In view of the above deficiencies in the prior art, the present invention provides a preparation method and application of a tumor-targeted photothermal / radiotherapy sensitizer, which has good POD-like enzyme activity and CAT-like enzyme activity and can solve the technical problem of being unable to effectively inhibit the growth of cancer cells due to the hypoxic tumor microenvironment.

[0007] To achieve the above object, the technical solution adopted by the present invention to solve its technical problems is as follows:

[0008] A preparation method of a tumor-targeted photothermal / radiotherapy sensitizer, which comprises the following steps:

[0009] (1) Prepare Fe3O4@C nanoparticles by a hydrothermal synthesis method;

[0010] (2) After dispersing the Fe3O4@C nanoparticles in a solution, add platinum acetylacetonate, and deposit Pt nanoparticles by thermal degradation in an atmosphere of a protective gas to obtain Fe3O4@C@Pt nanoparticles;

[0011] (3) Make the Fe3O4@C@Pt nanoparticles combine with a tumor-targeting ligand by electrostatic adsorption to obtain targeted tumor nano iron-platinum particles.

[0012] Further, in step (2), the mass ratio of the Fe3O4@C nanoparticles to platinum acetylacetonate is 0.5-1:1.

[0013] Further, in step (2), the mass ratio of the Fe3O4@C nanoparticles to platinum acetylacetonate is 1:1.

[0014] Further, in step (2), the thermal degradation temperature is 200-260 °C and the thermal degradation time is 1-1.5 h.

[0015] Further, in step (3), the Fe3O4@C@Pt nanoparticles and the tumor-targeting ligand are ultrasonically treated for 30-45 min under ice-water bath conditions and in an oxygen environment to complete electrostatic adsorption.

[0016] Further, the tumor-targeting ligand is cRGD-DSPE-PEG, and its preparation method is as follows:

[0017] It is obtained by mixing cRGD-SH and DSPE-PEG-SH in a mass ratio of 1:2 and adding 30% H2O2 and shaking for 24 h under dark conditions.

[0018] Further, the preparation method of the Fe3O4@C nanoparticles is as follows:

[0019] Ferrocene was added to an acetone solution. Subsequently, PEG 1000 and 30% H2O2 were added to the mixture, and magnetic stirring was carried out at room temperature. The transparent solution was transferred to a Teflon-lined stainless steel autoclave to collect the black product, obtaining Fe3O4@C nanoparticles.

[0020] The chemical formula of the nano iron-platinum particles prepared in the present invention is cRGD-HFPC-O2, and HFPC is hydrogenated Fe3O4@C@Pt. These nano iron-platinum particles contribute to the realization of multi-modal synergistic tumor therapy such as chemodynamic therapy, photothermal therapy, and chemodynamic therapy combined with radiotherapy, avoiding problems such as drug resistance and side effects caused by single chemotherapy drug treatment, and laying a material foundation for the efficient and safe diagnosis and treatment integration of tumor patients.

[0021] The nano iron-platinum particles prepared in the present invention have better POD-like enzyme activity and CAT-like enzyme activity compared with traditional iron-based nano materials. Their Fenton catalytic ability and photothermal conversion ability are significantly superior to those of Fe3O4 nanoparticles. In addition, the nano iron-platinum particles have good biocompatibility, showing no significant toxicity to normal cells, having the potential to target tumor sites and the ability to selectively kill tumor cells. The in vivo anti-tumor results also prove this point. After cRGD-HFPC-O2 is combined with 808 nm laser treatment, the tumors of mice are significantly inhibited, while the body weight and blood routine of mice have no obvious difference compared with the control group. Moreover, it can relieve the hypoxia inside the tumor, further enhancing the inhibitory effect of simple X-ray on tumors and having the effect of radiotherapy sensitization. Therefore, the nano iron-platinum particles contribute to the realization of multi-modal synergistic tumor therapy such as chemotherapy, chemodynamic therapy, and photothermal therapy, avoiding problems such as drug resistance and side effects caused by single chemotherapy drug treatment, and laying a material foundation for the efficient and safe diagnosis and treatment integration of tumor patients.

[0022] A tumor-targeted photothermal / radiotherapy sensitizer prepared by the above method.

[0023] Use of the above tumor-targeted photothermal / radiotherapy sensitizer in the preparation of a targeted drug for treating tumors.

[0024] Use of the above tumor-targeted photothermal / radiotherapy sensitizer in the preparation of a preparation with radiotherapy sensitization efficacy.

[0025] Advantages of the present invention:

[0026] In the present invention, Pt nanoparticles are deposited on the surface of Fe3O4@C nanoparticles in a high-boiling organic solvent through high-temperature thermal degradation. Nanoparticles with high catalytic performance, high photothermal performance, and high imaging performance are prepared according to the ratio of Fe3O4@C: platinum acetylacetonate = 1:1. Compared with traditional iron-based nanomaterials, the nanoparticles have better POD-like enzyme activity and CAT-like enzyme activity, and their Fenton catalytic ability and photothermal conversion ability are significantly superior to those of Fe3O4 nanoparticles. In addition, the nano iron-platinum particles have good biocompatibility, no significant toxicity to normal cells, and the ability to selectively kill tumor cells.

[0027] The in vivo anti-tumor results also prove this. After cRGD-HFPC-O2 combines with near-infrared light and X-ray treatment, the tumors of mice are significantly inhibited, and there is no obvious difference in the body weight and blood routine of mice compared with the control group. Therefore, the nano copper-iron-platinum particles contribute to the realization of multi-modal synergistic tumor treatment such as chemodynamic therapy, photothermal therapy, and chemodynamic therapy and radiotherapy, avoiding problems such as drug resistance and side effects caused by single chemotherapy drug treatment, and laying a material foundation for the efficient and safe diagnosis and treatment integration of tumor patients. Brief Description of the Drawings

[0028] Figure 1 are the electron microscopy images of different nanoparticles; among them, (a) TEM image of Fe3O4@C; (b) TEM image of HFCP; (c) TEM image of cRGD-HFCP-O2; (d) hydrodynamic sizes of Fe3O4@C, HFCP-O2, and cRGD-HFCP-O2;

[0029] Figure 2 are the detection results of the catalytic activities of different nanoparticles; among them, (a) UV-visible spectral analysis of ·OH generated by hydrogen peroxide catalyzed by HFCP-O2 in TMB solutions with different pH values; (b) UV-visible spectral analysis of ·OH generated by hydrogen peroxide catalyzed by Fe3O4, Fe3O4@C, and HFCP-O2; (c) O2 release curve of HFCP-O2 in water with or without 808 nm laser; (d) temperature change curve of different concentrations of cRGD-HFCP-O2 solution after 5 min of 808 nm laser irradiation;

[0030] Figure 3 shows the effect of cRGD-HFCP-O2 prepared in the present invention on cell viability; among them, (a) relative cell viability of 4T1 cells treated with different groups for 24 h; (b) relative cell viability of 293T cells treated with different concentrations for 24 h; (c) relative cell viability of CT26 cells treated with different concentrations; (d) relative cell viability of CT26 cells treated with different treatment groups;

[0031] Figure 4 Results of the co-treatment of cRGD-HFCP-O2 prepared according to the present invention and different treatment methods on tumors; wherein, (a) Changes in tumor volume of tumor-bearing mice in different treatment groups in combination with 808 nm laser; (b) Changes in mouse body weight; (c) Changes in tumor volume of tumor-bearing mice in different treatment groups in combination with X-rays; (d) Changes in mouse body weight;

[0032] Figure 5 Safety detection of cRGD-HFCP-O2 prepared according to the present invention; wherein, (a) Hemolysis pictures of cRGD-HFCP-O2 at different concentrations and ultraviolet-visible absorption spectra of the red blood cell supernatant after treatment with cRGD-HFCP-O2; (b) Routine blood analysis data 24 h and 48 h after injection of cRGD-HFCP-O2. Specific embodiments

[0033] The specific embodiments of the present invention will be described below to facilitate the understanding of the present invention by those skilled in the art of the present technology. However, it should be clear that the present invention is not limited to the scope of the specific embodiments. For those skilled in the art of the present technology, as long as various changes are within the spirit and scope of the present invention defined and determined by the appended claims, these changes are obvious, and all inventions and creations using the concept of the present invention are within the scope of protection.

[0034] Example 1 Synthesis of cRGD-HFCP-O2 nanomaterial

[0035] 1. Synthesis of Fe3O4@C nanoparticles: Hydrothermal method was used to prepare Fe3O4@C nanomaterials. Ferrocene (0.8 g) and acetone (60 mL) were placed in a conical flask and stirred for 30 min, then polyethylene glycol 1000 (PEG 1000, 1 g) was added and stirred for 30 min, and then 3 mL of H2O2 was added and stirred for 30 min. The above mixed solution was transferred to a high-pressure reaction kettle, sealed and placed in an oven. When the temperature was raised to 200 °C, the timing was 48 h. After the reaction was completed, the reactants were centrifuged at 11000 rpm for 10 min to collect the precipitate, and then washed 3 times with absolute ethanol and deionized water. Finally, the product was dispersed in deionized water and treated in an ultrasonic instrument for 10 min to obtain a uniformly dispersed suspension of Fe3O4@C nanoparticles.

[0036] 2. Preparation of Fe3O4@C@Pt (FCP) nanoparticles: The Fe3O4@C nanoparticles were centrifuged and redispersed in triethylene glycol, and then quantified by inductively coupled plasma emission spectrometry (ICP). The Fe ion content of the quantified Fe3O4@C and platinum acetylacetonate were added to a three-necked flask in a ratio of 1:1. PVPK30 (0.5 g) was added, and then the triethylene glycol solution was made up to 30 mL. The reaction device was fixed to a heating stirrer, and N2 was passed below the liquid surface. When the temperature rose to 260 °C, timing started for 90 min. After the reaction ended, the solution temperature was lowered to room temperature, centrifuged, and the precipitate was washed 3 times with absolute ethanol and deionized water. Finally, the product was dispersed in deionized water and placed in an ultrasonic instrument for 10 min to obtain the reactant Fe3O4@C@Pt (FCP) nanoparticles.

[0037] 3. Preparation of HFCP-O2 nanoparticles: NaBH4 (35 mg) was dissolved in deionized water (5 mL) and left in the refrigerator overnight. Then, 10 mg of Fe3O4@C@Pt nanoparticles were mixed with 5 mL of the NaBH4 solution and placed in an ultrasonic bath. After ultrasonic treatment for 1 h, the reaction product was transferred to a centrifuge tube and centrifuged at 11000 rpm for 10 min to collect the precipitate product. The precipitate was washed 3 times with deionized water. Finally, the product was dispersed in deionized water and placed in an ultrasonic instrument for 10 min to obtain H-Fe3O4@C@Pt (HFCP) nanoparticles. Finally, O2 was introduced into the HFCP solution to obtain the HFCP-O2 nanomaterial.

[0038] 4. Preparation of cRGD-HFCP-O2: First, DSPE-PEG-SH (5 mg) and cRGD-SH (5 mg) were dissolved in deionized water. The solution was taken in a ratio of 2:1 and mixed with H2O2 (30%) and shaken overnight in a shaker to obtain cRGD-DSPE-PEG. Then, the HFCP-O2 into which O2 had been introduced was mixed with cRGD-DSPE-PEG in a ratio of 2:1 and ultrasonicated in an ultrasonic bath for 30 min. The reaction product was transferred to a centrifuge tube and centrifuged at 11000 rpm for 10 min to collect the precipitate product. The precipitate was washed 3 times with deionized water. Finally, the product was dispersed in 15 mL of deionized water and placed in an ultrasonic instrument for 10 min to obtain the cRGD-HFCP-O2 nanomaterial, which was stored in a refrigerator at 4 °C.

[0039] Example 2 Morphology Detection

[0040] For the synthesized cRGD-HFCP-O2 nanoparticles of the present invention, the morphology of the nanoparticles was observed using a transmission electron microscope (TEM), and the results are shown in Figure 1 .

[0041] AsFigure 1 As shown, the Fe3O4@C nanoparticles have a relatively regular core-shell structure, with a size of 150 - 200 nm, and are evenly dispersed without obvious agglomeration. Based on this, Pt nanoparticles are deposited on the surface of the Fe3O4@C nanoparticles by the principle of high-temperature thermal degradation. The Pt nanoparticles are evenly deposited on the surface of the Fe3O4@C nanoparticles. After deposition, the HFCP nanoparticles are circular and evenly dispersed, indicating that the nanoparticles still have good monodispersity after Pt deposition. By functionalizing the surface of the HFCP nanoparticles with cRGD-DSPE-PEG, the tumor targeting of the nanomaterial is imparted, and the dispersibility of the nanomaterial is further improved. After functional modification, the cRGD-HFCP-O2 nanomaterial is circular, evenly dispersed, with uniform particle size and shape, and a particle size of 200 nm. The results of dynamic light scattering (DLS) measurements show that the Fe3O4@C nanoparticles exhibit good monodispersity in aqueous solution, with a relatively uniform particle size distribution and an average particle size of 200 nm. The DLS results are highly consistent with the nanoparticle sizes observed by transmission electron microscopy (TEM), further verifying the structural stability of the Fe3O4@C nanoparticles. After depositing Pt particles on the surface of the Fe3O4@C nanoparticles, the particle size changes. After functional modification with cRGD-DSPE-PEG, the water solubility and dispersibility of the nanoparticles become better, and the particle size also changes.

[0042] Example 3 Catalytic Activity Detection

[0043] The catalytic activity of the synthesized cRGD-HFCP-O2 nanoparticles of the present invention was analyzed by TMB colorimetric experiments, and the effect of PBS buffers with different pH values on the Fenton catalytic activity of HFCP-O2 was studied. The results are shown in Figure 2 .

[0044] As Figure 2 shown, at pH = 5.5, the higher the absorbance of HFCP-O2, the lower the absorbance as the pH increases, indicating that the Fenton catalytic activity of HFCP-O2 is higher under acidic conditions. At the same time, this also shows that HFCP-O2 has pH-responsive ability; The release of O2 in water by the HFCP-O2 nanoparticles with and without laser irradiation was studied using a portable dissolved oxygen meter.

[0045] Under the irradiation of 808 laser, it helps to improve the catalase (CAT) catalytic activity of HFCP-O2, and the release of O2 in water increases. It can be seen from this that HFCP-O2 has good catalase catalytic activity. The photothermal performance of cRGD-HFCP-O2 nanoparticles in vitro was observed using a photothermal imager. It was found that as the concentration of the nanoparticles increased, the temperature of the cRGD-HFCP-O2 nanoparticles also gradually increased. When the concentration was 200 μg / mL, the temperature could exceed 65 °C, and as the power of the 808 nm laser increased, the temperature of the cRGD-HFCP-O2 solution gradually increased, indicating that the cRGD-HFCP-O2 nanoparticles have good photothermal performance.

[0046] Example 4 Detection of the Efficacy of cRGD-HFCP-O2

[0047] 1. In vitro safety assessment

[0048] The biosafety of nanoparticles is an important consideration in evaluating their potential for clinical application. The results showed that the magnetic nanoparticles had low cytotoxicity to 293T cells, and the survival rate exceeded 70% in the concentration range of 0 - 24 mg / mL, indicating that the cRGD-HFCP-O2 nanoparticles had low toxicity to normal cells ( Figure 3 b).

[0049] 2. Evaluation of the in vitro anti-tumor efficacy in combination with 808 nm laser

[0050] Four control groups were set up, namely HFCP, HFCP-O2, cRGD-HFCP-O2, and cRGD-HFCP-O2 plus laser (cRGD-HFCP-O2+L), to evaluate the viability of 4T1 cells treated with different groups.

[0051] As Figure 3 shown in a, as the concentration increased, the survival rate of 4T1 cells cultured with different treatments decreased. More importantly, compared with cRGD-HFCP-O2, cRGD-HFCP-O2+L had a stronger inhibitory effect on cell viability, which was due to the fact that when the laser was used, the temperature increase would burn the tumor cells.

[0052] 3. Evaluation of the in vitro anti-tumor efficacy in combination with X-ray

[0053] CT26 cells were cultured with different concentrations of Fe3O4@C+RT group, HFCP-O2+RT group, and cRGD-HFCP-O2+RT group for 24 h, and then the killing effect on CT26 cells after different treatments was detected.

[0054] As Figure 3As shown in c and d, the killing effect of cRGD-HFCP-O2+RT on CT26 cells was the strongest. As the concentration of the nanomaterial increased, the relative cell survival rate of cancer cells decreased. This indicates that the nanoparticles have a cell-killing effect on tumor cells. Then we found that the killing effect of simple X-ray on tumor cells at 4 Gy was very weak, but after the nanomaterial entered the cells, the effect of simple X-ray was enhanced, greatly strengthening the killing effect on tumor cells, indicating that the cRGD-HFCP-O2 nanomaterial has the effect of enhancing simple radiotherapy, that is, it has the effect of radiotherapy sensitization.

[0055] Experimental Example 5 Detection of the Synergistic Efficacy of cRGD-HFCP-O2

[0056] 1. Evaluation of the in vivo anti-tumor efficacy of the combination with 808 nm laser

[0057] To evaluate the in vivo anti-tumor effect of the combination of cRGD-HFPC-O2 and 808 nm laser, the following steps were specifically included:

[0058] 4T1 cells (5×10 5 cells / mouse) were subcutaneously injected into the right hind leg of female Balbc mice to establish a tumor model. After inoculation, the tumor volume was monitored. When the tumor volume was approximately 100 mm 3 , treatment began. The tumor-bearing mice were randomly divided into 5 groups (n = 5): (a) PBS, (b) HFPC, (c) HFPC-O2, (d) cRGD-HFPC-O2, (e) cRGD-HFPC-O2+L. The mice were injected with the drug once every two days through the tail vein, and the body weight and tumor volume of the mice were recorded every other day.

[0059] As Figure 4 shown in a, the inhibition of tumor proliferation by cRGD-HFPC-O2 nanoparticles was very limited. However, under the synergistic effect of the 808 nm laser, cRGD-HFPC-O2 showed a strong tumor suppression ability, and the tumor tissue of the mice was almost completely ablated, indicating that the use of laser can further inhibit tumor growth.

[0060] 2. Evaluation of the in vivo anti-tumor efficacy of the combination with X-ray

[0061] To evaluate the radiosensitizing antitumor ability of cRGD-HFCP-O2 in vivo, CT26 cells were inoculated into the right upper leg of BALB / c mice by subcutaneous injection to construct BALB / c mice bearing subcutaneous CT26 tumors. The tumor-bearing mice were randomly divided into 5 groups (n = 5): (a) PBS, (b) RT, (c) Fe3O4@C + RT, (d) HFPC-O2 + RT, (e) cRGD-HFCP-O2 + RT. Then, PBS, Fe3O4@C, HFCP-O2, and cRGD-HFCP-O2 nanoparticles were injected via the tail vein, and 12 h later, X-ray irradiation (4 Gy) was performed.

[0062] As Figure 4 shown in c, simple X-ray has the effect of inhibiting tumor growth, indicating that radiotherapy has anti-cancer activity. Compared with the RT group, the cRGD-HFCP-O2 + RT group showed the most significant inhibition of tumor growth, enhancing the simple radiotherapy effect, and cRGD-HFCP-O2 has the effect of radiosensitization. From the results, the cRGD-HFCP-O2 + RT group showed the strongest anti-cancer activity, suggesting that X-ray synergistically further inhibited tumor growth.

[0063] 3. In vivo safety evaluation

[0064] As a new therapeutic drug, in addition to its efficacy, its safety also needs to be systematically evaluated in vivo. During the treatment process, the body weights of mice in different groups were monitored, and there were no significant differences in the body weights of mice in each group, indicating that systemic toxicity can be ignored ( Figure 4 b, d).

[0065] Example 6 Safety detection of cRGD-HFCP-O2

[0066] The hemolysis rate and blood routine of the nanoparticles were detected to verify the safety of cRGD-HFCP-O2 nanoparticles, and the results are shown in Figure 5 .

[0067] As Figure 5 shown in a, when the concentration range of cRGD-HFCP-O2 was 0 - 200 μg / mL, the hemolysis rate was still lower than 5%, and there was no obvious damage to red blood cells, indicating that cRGD-HFCP-O2 has good blood compatibility. In addition, compared with the PBS group, there were no obvious abnormalities in the blood routine indexes of mice after injection of cRGD-HFCP-O2, indicating that cRGD-HFCP-O2 has good biocompatibility ( Figure 5 b). Further, it shows that the prepared cRGD-HFCP-O2 of the present invention has good blood biocompatibility and has potential clinical application potential in cancer treatment.

[0068] Finally, it should be noted that the above specific embodiments are only used to illustrate the technical solutions of the present invention rather than to limit them. Although the present invention has been described in detail with reference to the examples, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and all of them should be covered by the scope of the claims of the present invention.

Claims

1. A preparation method of a tumor-targeted photothermal / radiotherapy sensitizer, characterized in that, It includes the following steps: (1) Prepare Fe3O4@C nanoparticles by hydrothermal synthesis method; (2) After dispersing the Fe3O4@C nanoparticles in a solution, add platinum acetylacetonate, and deposit Pt nanoparticles by thermal degradation in an atmosphere of protective gas to obtain Fe3O4@C@Pt nanoparticles; (3) Make the Fe3O4@C@Pt nanoparticles combine with tumor-targeting ligands by electrostatic adsorption to obtain tumor-targeted nano iron-platinum particles.

2. The preparation method according to claim 1, wherein In step (2), the mass ratio of Fe3O4@C nanoparticles to platinum acetylacetonate is 0.5 - 1:

1.

3. The preparation method according to claim 2, characterized in that, In step (2), the mass ratio of Fe3O4@C nanoparticles to platinum acetylacetonate is 1:

1.

4. The preparation method according to claim 1, wherein In step (2), the thermal degradation temperature is 200 - 260 °C, and the thermal degradation time is 1 - 1.5 h.

5. The preparation method according to claim 1, characterized in that, In step (3), the electrostatic adsorption of Fe3O4@C@Pt nanoparticles and tumor-targeting ligands is completed by ultrasonic treatment for 30 - 45 min in an oxygen environment under an ice-water bath condition.

6. The preparation method according to claim 1 or 5, characterized in that, The tumor-targeting ligand is cRGD-DSPE-PEG, and its preparation method is: It is obtained by mixing cRGD-SH and DSPE-PEG-SH according to a mass ratio of 1:2 and adding 30% H2O2 and shaking for 24 h in the dark.

7. The preparation method according to claim 1, wherein The preparation method of Fe3O4@C nanoparticles is as follows: Add ferrocene into an acetone solution, and then add PEG 1000 and 30% H2O2 into the mixture, perform magnetic stirring at room temperature, transfer the transparent solution and collect the black product to obtain Fe3O4@C nanoparticles.

8. A tumor-targeted photothermal / radiotherapy sensitizer, characterized in that, It is prepared by using the method described in any one of claims 1 - 7.

9. Use of the tumor-targeted photothermal / radiotherapy sensitizer according to claim 8 in the preparation of a targeted drug for treating tumors.

10. Use of the tumor-targeted photothermal / radiotherapy sensitizer according to claim 8 in the preparation of a preparation with radiotherapy sensitization efficacy.

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