A ruthenium-containing high molecular polymer, a preparation method and application thereof

Abstract

This invention belongs to the field of biomedical technology, specifically relating to a ruthenium-containing polymer, its preparation method, and its applications. The ruthenium-containing polymer provided by this invention is obtained by polymerization of a dibromohexacoordinate ruthenium complex, a photoresponsive dibromo monomer, a reactive oxygen species (ROS)-responsive dibromo monomer, and a bistin monomer under a catalyst catalysis. The catalyst includes a palladium-containing catalyst. The dibromohexacoordinate ruthenium complex has a central ruthenium element, with three dinitrogen ligands coordinated to the ruthenium element, wherein at least one nitrogen ligand has at least two Br groups. The photoresponsive dibromo monomer has a conjugated structure and at least two Br groups. The ROS-responsive dibromo monomer has chemical bonds that can be broken in response to ROS and at least two Br groups. The bistin monomer has at least two trimethyltin groups. This ruthenium-containing polymer is biodegradable, has high yield, good reproducibility, exhibits near-infrared light response, combines photothermal and photodynamic functions, and has a simple synthesis method.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and specifically relates to a ruthenium-containing polymer, its preparation method, and its application. Background Technology

[0002] Photoresponsive polymers have broad application prospects in optoelectronic devices, sensing, and biomedicine. Among them, materials that can be excited by near-infrared light with strong tissue penetration are particularly important. Ruthenium complexes, due to their excellent photophysical and chemical properties, such as long excited-state lifetimes, high photostability, and good biocompatibility, have been widely studied as photosensitizers and luminescent probes.

[0003] However, most existing ruthenium-containing polymer materials have the following problems: 1. Non-degradability: Many ruthenium-based polymers are difficult to degrade and metabolize in vivo, which may cause long-term toxicity or immune responses, limiting their clinical translation.

[0004] 2. Single function: Most materials only focus on one function of photothermal (PTT) or photodynamic therapy (PDT), making it difficult to achieve efficient synergistic treatment.

[0005] 3. Complex synthesis: The preparation method is cumbersome, the yield is low, and the reproducibility is poor, which is not conducive to large-scale production and application.

[0006] 4. Inadequate excitation light source: Many materials require ultraviolet or visible light excitation, but these light sources have limited tissue penetration depth and pose a potential photodamage to normal tissue.

[0007] Therefore, developing a novel ruthenium-containing polymer material that is easy to synthesize, biodegradable, has near-infrared light response, and integrates photothermal and photodynamic functions is of great scientific significance and practical application value. Summary of the Invention

[0008] The purpose of this invention is to provide a ruthenium-containing polymer, its preparation method, and its applications. This ruthenium-containing polymer is biodegradable, has a high yield, good reproducibility, exhibits near-infrared light response, integrates photothermal and photodynamic functions, and has a simple synthesis method.

[0009] The first aspect of the present invention provides a ruthenium-containing polymer, wherein the ruthenium-containing polymer is obtained by Stille coupling polymerization of dibromohexacoordinate ruthenium complex, photoresponsive dibromo monomer, reactive oxygen species (ROS) responsive dibromo monomer and ditin monomer under the catalysis of a catalyst; The catalyst includes a palladium-containing catalyst; The dibromohexacoordinate ruthenium complex has a ruthenium metal element at its center, and three dinitrogen-containing ligands coordinate around the ruthenium metal element to form a hexacoordinate ruthenium complex, wherein at least one nitrogen-containing ligand has at least two Br groups; The photoresponsive dibromo monomer has a conjugated structure and at least two Br groups; The reactive oxygen species-responsive dibromo monomer has chemical bonds that can be broken in response to reactive oxygen species and at least two Br groups; The bistin monomer has at least two trimethyltin groups.

[0010] In some alternative embodiments, the catalyst comprises tris(o-methylphenyl)phosphine and tris(dibenzylideneacetone)dipalladium(O); In some optional embodiments, the molar ratio of tris(o-methylphenyl)phosphine to tris(dibenzylacetone)palladium(O) is (16-20):(4-5); In some optional embodiments, the total molar amount of the dibromohexacoordinate ruthenium complex, the photoresponsive dibromo monomer, the reactive oxygen species (ROS) responsive dibromo monomer, and the ditin monomer is in the ratio of the total molar amount of the catalyst to (19-22):1.

[0011] In some optional embodiments, the total molar amount of the dibromohexacoordinate ruthenium complex, the photoresponsive dibromo monomer, and the reactive oxygen species responsive dibromo monomer is in the molar ratio of the ditin monomer to 1:(1-1.1); preferably, the total molar amount of the dibromohexacoordinate ruthenium complex, the photoresponsive dibromo monomer, and the reactive oxygen species responsive dibromo monomer is in the molar ratio of the ditin monomer to 1:1. In some optional embodiments, the molar ratio of the dibromohexacoordinate ruthenium complex, the photoresponsive dibromo monomer, and the reactive oxygen species responsive dibromo monomer is (0.5~1.5):(0.5~1.5):0.5; In some alternative embodiments, the chemical bonds that are responsive to reactive oxygen species breaking include thioketone bonds or diselenide bonds.

[0012] In some alternative embodiments, the dibromohexacobalt ruthenium complex is selected from one of the following compounds: ; In some alternative embodiments, the photoresponsive dibromo monomer is selected from one of the following compounds: .

[0013] In some alternative embodiments, the bistin monomer is selected from one of the following compounds: ; In some alternative embodiments, the reactive oxygen species-responsive dibromo monomer is selected from one of the following compounds: .

[0014] In some alternative embodiments, the ruthenium-containing polymer includes a dibromohexacoordinate ruthenium complex monomer unit, a photoresponsive dibromo monomer unit, a reactive oxygen species responsive dibromo monomer unit, and a ditin monomer unit.

[0015] In some optional embodiments, the total molar amount of the dibromohexacoordinate ruthenium complex monomer unit, the photoresponsive dibromo monomer unit, and the reactive oxygen species responsive dibromo monomer unit is in the molar ratio of the ditin monomer unit to 1:(1-1.1); preferably, the total molar amount of the dibromohexacoordinate ruthenium complex monomer unit, the photoresponsive dibromo monomer unit, and the reactive oxygen species responsive dibromo monomer unit is in the molar ratio of the ditin monomer unit to 1:1. In some optional embodiments, the molar ratio of the dibromohexacoordinate ruthenium complex monomer unit, the photoresponsive dibromo monomer unit, and the reactive oxygen species responsive dibromo monomer unit is (0.5~1.5):(0.5~1.5):0.5; In some alternative embodiments, the dibromohexacoordinate ruthenium complex monomer unit is selected from the structures shown in any of the following formulas 1-1 to 1-14: ; In some alternative embodiments, the photoresponsive dibromomonounit is selected from the structures shown in any of the following formulas 1-15 to 1-17: .

[0016] In some alternative embodiments, the bis-tin monomer is selected from the structures shown in any of the following formulas 1-18 to 1-22: ; In some alternative embodiments, the reactive oxygen species-responsive dibromomon is selected from the structures shown in any of Formulas 1-23 to 1-24: .

[0017] In some alternative embodiments, the ruthenium-containing polymer comprises a structure as shown in any one of Formulas 1 to 30:

[0018] ; Wherein, the molar ratio of x, y and z is (0.5~1.5):(0.5~1.5):0.5; The preferred molar ratio of x, y and z is 1:1:0.5.

[0019] In the structural formula of this invention, R indicates that the two monomer units connected thereto are randomly arranged on the polymer backbone, and x, y, and z are the total molar percentages of the blocks within the brackets.

[0020] A second aspect of the present invention provides a method for preparing the above-mentioned ruthenium-containing polymer, comprising the following steps: Stille coupling polymerization was carried out in a solvent with the addition of a catalyst using the aforementioned dibromohexacoordinate ruthenium complex, photoresponsive dibromo monomer, reactive oxygen species (ROS) responsive dibromo monomer, and ditin monomer.

[0021] In some alternative embodiments, the solvent includes toluene; In some alternative embodiments, the Stille polymerization reaction is carried out under an inert gas atmosphere; In some alternative embodiments, the Stille polymerization reaction is carried out at a temperature of 90-110°C.

[0022] In some optional embodiments, the Stille polymerization reaction is terminated after 4-10 minutes. Preferably, the Stille polymerization reaction is terminated after 5 minutes.

[0023] A third aspect of the present invention provides the use of the above-described ruthenium-containing polymer or the ruthenium-containing polymer prepared by the above-described preparation method in the preparation of a medicament for treating tumors; In some alternative embodiments, the drug for treating tumors includes drugs for photothermal therapy and / or photodynamic therapy of tumors.

[0024] A fourth aspect of the present invention provides a nanoparticle comprising: a) an amphiphilic carrier; b) the above-described ruthenium-containing polymer or the ruthenium-containing polymer prepared by the above-described preparation method; In some alternative embodiments, the amphiphilic carrier includes methoxy polyethylene glycol-distearate phosphatidylethanolamine (mPEG-DSPE), distearate phosphatidylethanolamine-diethylenetriaminepentaacetic acid (DSPE-DTPA), and methoxy poly(2-ethyl-2-oxazoline)-polylactic acid-glycolic acid copolymer (mPEOz-PLGA). Compared with the prior art, the technical solution of the present invention has at least the following advantages: 1. The ruthenium-containing polymer provided by this invention is a photoresponsive, biodegradable pseudoconjugated polymer. This ruthenium-containing polymer is a tumor microenvironment-responsive monomer that can degrade in high ROS environments, exhibiting better biocompatibility. This ruthenium-containing polymer also possesses near-infrared photoresponsiveness, combining photothermal and photodynamic therapies for highly efficient synergistic treatment.

[0025] 2. The ruthenium-containing polymer provided by this invention has a simple synthesis method, low raw material cost, high yield, high product stability, and good reproducibility. Attached Figure Description

[0026] Various other advantages and benefits will become apparent to those skilled in the art upon reading the following detailed description of preferred embodiments. The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. In the drawings: Figure 1The ruthenium-containing polymer of Formula 1 prepared in Example 1 1 H NMR spectrum; Figure 2 The ruthenium-containing polymer of Formula 2 prepared in Example 2 1 H NMR spectrum; Figure 3 The ruthenium-containing polymer of Formula 3 prepared in Example 3 1 H NMR spectrum; Figure 4 The particle size distribution of the nanoparticles prepared in Example 4 is shown in the diagram. Figure 5 The ultraviolet absorption spectrum of the ruthenium-containing polymer of Formula 3 prepared in Example 3; Figure 6 The concentration standard curve of the ruthenium-containing polymer of Formula 3 prepared in Example 3; Figure 7 Photothermal imaging of the nanoparticles prepared in Example 4; Figure 8 The photothermal heating curve of the nanoparticles prepared in Example 4; Figure 9 The photothermal stability curve of the nanoparticles prepared in Example 4; Figure 10 ESR spectrum of hydroxyl radicals generated by nanoparticles prepared in Example 4; Figure 11 The singlet oxygen ESR spectrum was generated for the nanoparticles prepared in Example 3; Figure 12 DPBF image of the nanoparticles prepared in Example 3; Figure 13 This is a line graph comparing the cell survival rates of C666 cells treated with the nanoparticles prepared in Example 3. Detailed Implementation

[0027] Exemplary embodiments of the invention will now be described in more detail with reference to the accompanying drawings. While exemplary embodiments of the invention are shown in the drawings, it should be understood that the invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the invention and to fully convey the scope of the invention to those skilled in the art.

[0028] It should be understood that the terminology used herein is for the purpose of describing particular exemplary embodiments only and is not intended to be limiting. Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “described” as used herein may also mean including the plural forms. The terms “comprising,” “including,” “containing,” and “having” are inclusive.

[0029] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, this invention can be implemented using any prior art methods, apparatus, and materials similar to or equivalent to those described in the embodiments of this invention, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention.

[0030] The technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art. Unless otherwise specified, the experimental reagents used in the following embodiments are all conventional biochemical reagents; the raw materials, instruments, and equipment used in the following embodiments can all be obtained commercially or through existing methods; unless otherwise specified, the amounts of experimental reagents used are the amounts used in conventional experimental operations; unless otherwise specified, the experimental methods are all conventional methods.

[0031] It should be further noted that the following description is merely exemplary and used to illustrate the present invention, and not to limit the specific scope of the invention. Furthermore, the selected comparative solutions are intended to demonstrate the superiority of the present invention's technical solutions, and do not necessarily represent prior art in this technical field.

[0032] Example 1 This embodiment provides a method for preparing a ruthenium-containing polymer (as shown in Formula 1), and the synthetic route includes the following: ; The specific synthesis steps include the following: Monomer 1 (80 mg, 0.1 mmol), monomer 15 (66.8 mg, 0.1 mmol), monomer 18 (213.2 mg, 0.25 mmol), monomer 23 (28.8 mg, 0.05 mmol), tris(o-methylphenyl)phosphine (6.2 mg, 0.02 mmol), and tris(dibenzylacetone)palladium(O) (4.6 mg, 0.005 mmol) were dissolved in 3 mL of toluene under nitrogen protection at 110 °C. The reaction was monitored with methanol. After 5 minutes, the liquid in the reaction system was injected into a large amount of methanol using a syringe, centrifuged, and the solid was retained. The solid was washed three times with methanol and dried to obtain the ruthenium-containing polymer shown in Formula 1. The x:y:z ratio was 1:1:0.5. 1 HNMR (MHz, deuterated chloroform) spectrum as shown Figure 1 Show.

[0033] Example 2 This embodiment provides a method for preparing a ruthenium-containing polymer (as shown in Formula 2), and the synthetic route includes the following: ; Specifically, the steps include the following: Monomer 2 (80 mg, 0.1 mmol), monomer 15 (68.8 mg, 0.1 mmol), monomer 18 (219.3 mg, 0.258 mmol), monomer 23 (29.6 mg, 0.051 mmol), tris(o-methylphenyl)phosphine (6.3 mg, 0.02 mmol), and tris(dibenzylacetone)palladium(O) (4.7 mg, 0.005 mmol) were dissolved in 3 mL of toluene under nitrogen protection at 110 °C. The reaction was monitored with methanol. After 5 minutes, the liquid in the reaction system was injected into a large amount of methanol using a syringe, centrifuged, and the solid was retained. The solid was washed three times with methanol and dried to obtain the ruthenium-containing polymer shown in Formula 2. The x:y:z ratio was 1:1:0.5. 1 HNMR (MHz, deuterated chloroform) spectrum as shown Figure 2 As shown.

[0034] Example 3 This embodiment provides a method for preparing a ruthenium-containing polymer (as shown in Formula 3), and the synthetic route includes the following: ; Specifically, the steps include the following: Monomer 3 (100 mg, 0.086 mmol), monomer 15 (58 mg, 0.086 mmol), monomer 18 (184.8 mg, 0.216 mmol), monomer 23 (25 mg, 0.044 mmol), tris(o-methylphenyl)phosphine (5.2 mg, 0.017 mmol), and tris(dibenzylacetone)palladium(O) (4 mg, 0.004 mmol) were dissolved in 3 mL of toluene under nitrogen protection and reacted at 110 °C. The reaction was monitored with methanol. After 5 minutes, the liquid in the reaction system was injected into a large amount of methanol using a syringe, centrifuged, and the solid was retained. The solid was washed three times with methanol and dried to obtain the ruthenium-containing polymer shown in Formula 3. The x:y:z ratio was 1:1:0.5. 1 The 1H NMR (MHz, deuterated chloroform) spectrum is shown below. Figure 3 As shown.

[0035] Example 4: Preparation of Nanoparticles 10 mg of the ruthenium-containing polymer (as shown in Formula 3) prepared in Example 3 and 100 mg of mPEG-DSPE (Mw 2000) were weighed and dissolved in 10 mL of tetrahydrofuran (THF) to obtain a polymer solution. 100 mL of deionized water was added to a 200 mL Erlenmeyer flask, which was placed on a magnetic stirrer at 600 rpm. The polymer solution was slowly added dropwise to the flask using a 1 mL dropper. After the addition was complete, the flask was dialyzed for 12 h using a dialysis bag with a molecular weight cutoff of 8000. The dialysate was filtered through a 220 μm filter membrane to prepare a nanoparticle solution. The particle size of the nanoparticles was determined using dynamic light scattering (DLS), and the results are shown in the attached figure. Figure 4 As shown, its average particle size is 115.6 nm and its polymer dispersity index (PDI) is 0.15.

[0036] Example 5: Ultraviolet Absorption Spectroscopy Characterization Accurately weigh 1 mg of the ruthenium-containing polymer synthesized in Example 3 and dissolve it in 10 mL of tetrahydrofuran (THF) to prepare a polymer stock solution of 100 μg / mL. Dilute the stock solution with THF to seven concentration gradients: 60 μg / mL, 50 μg / mL, 40 μg / mL, 30 μg / mL, 20 μg / mL, 10 μg / mL, and 0 μg / mL. The ultraviolet absorption spectrum was detected using a Lambda 1050+ UV-Vis-NIR spectrophotometer, and the results are shown in the attached figure. Figure 5 As shown.

[0037] Example 6: Quantitative Analysis of Nanoparticle Polymer Concentration The absorbance value at 958 nm of the ultraviolet absorption spectrum measured in Example 5 was used to plot an absorbance-concentration curve. A standard curve for the concentration of the ruthenium-containing polymer was then obtained by fitting the curve, as shown in the attached figure. Figure 6 As shown. For the quantitative detection of the ruthenium-containing polymer content in the nanoparticle solution prepared in Example 4, the nanoparticle solution prepared in Example 4 was mixed with THF at a ratio of 1:9 to redissolve the nanoparticles into a ruthenium-containing polymer solution. The content of the ruthenium-containing polymer in the nanoparticles was calculated by measuring the ultraviolet absorption spectrum of the redissolved solution and substituting the absorbance value at 958 nm into the standard curve.

[0038] Example 7: Characterization of photothermal properties of nanoparticles The nanoparticle solution prepared in Example 4 was quantified according to the method in Example 6. Then, using the concentration of the ruthenium-containing polymer as the effective concentration, the nanoparticle solution was diluted with water to six concentration gradients: 100 μg / mL, 50 μg / mL, 30 μg / mL, 10 μg / mL, 5 μg / mL, and 0 μg / mL. Thermal images and temperature rise curves of nanoparticles at different concentrations irradiated with a 980 nm laser were recorded using an infrared thermal imager for 10 min. The results of the thermal images of nanoparticles at different concentrations irradiated with a 980 nm laser are shown below. Figure 7 As shown, the temperature rise curves of nanoparticles with different concentrations irradiated by a 980nm laser are as follows: Figure 8 As shown. A cycle of 5 minutes of heating followed by 11 minutes of cooling was performed, repeated five times. The photothermal stability of the nanoparticles in Example 4 was measured using an infrared thermal imager, and the results are as follows. Figure 9 As shown, the nanoparticles exhibit excellent photothermal stability.

[0039] Example 8: Photodynamic Performance Characterization The nanoparticle solution prepared in Example 4 was used to determine the types of reactive oxygen species (ROS) using electron spin resonance spectroscopy (ESR). After mixing the ROS scavenger with the nanoparticles, the system was irradiated with a 980 nm laser. The ESR spectrum showed four peaks after 5,5-dimethyl-1-pyrrolline-N-oxide (DMPO) was used to scavenge hydroxyl radicals (•OH), as shown in the attached figure. Figure 10 As shown. Singlet oxygen was captured using 2,2,6,6-tetramethylpiperidine (TEMP). 1 The O2 content was then reflected in the ER spectrum, showing three peaks, as shown in the attached figure. Figure 11 As shown.

[0040] Characterized using DPBF (1,3-diphenylisobenzofuran) method 1 The ability to generate O2. DPBF is a singlet oxygen indicator fluorescent probe, for... 1 O2 has high specificity. Once it interacts with... 1 O2 binding irreversibly oxidizes DPBF, causing a rapid decrease in absorption intensity at 410 nm in the UV-Vis spectrum. The NP+L group mixed DPBF with nanoparticles in an appropriate ratio to ensure the OD value of the microplate reader was between 1.0 and 1.2. Irradiation with a 980 nm laser was used, and absorbance values ​​were read every minute. The rate of decrease in the curve represents... 1 The O2 generation capacity was measured, and a control group (DPBF+L group) without added nanoparticles was also included. The test results are attached. Figure 12 As shown, NP+L represents the NP+L group, DPBF+L represents the DPBF+L group, and A / A0 refers to the absorbance value at 410nm divided by the initial absorbance value.

[0041] Example 9 Nanoparticle Cytotoxicity The anticancer activity of nanoparticles was evaluated through in vitro cancer cell toxicity experiments, and the effect of photodynamic therapy with nanoparticles was investigated. The experimental groups were designed as follows: PBS+L group, NP group, and NP+L group. The conditions for the photodynamic therapy group were: wavelength 980 nm, power 1.0 W / cm². 2 The illumination time for each hole is 3 minutes.

[0042] Specifically, it includes: Evenly spread approximately 8×10 mm of material in each well of the 96-well plate. 3 C666 cells were incubated at 37°C for 12 h in a constant temperature cell culture incubator. After cell adhesion and growth, the NP group was treated with 10 μL of nanoparticle solutions of different concentrations obtained in Example 4 (based on the concentration of ruthenium-containing polymer, the effective concentrations were 0.05 μg / mL, 0.5 μg / mL, 5 μg / mL, 10 μg / mL, 20 μg / mL, and 40 μg / mL) for 24 h; the NP+L group was treated with 10 μL of nanoparticle solutions of different concentrations obtained in Example 4 (based on the concentration of ruthenium-containing polymer, the effective concentrations were 0.05 μg / mL, 0.5 μg / mL, 5 μg / mL, 10 μg / mL, 20 μg / mL, and 40 μg / mL) for 12 h, and then cultured at a wavelength of 980 nm and a power of 1.0 W / cm². 2 The group was treated with light for 3 min, followed by 12 h of further treatment; the PBS+L group was treated with 10 μL of phosphate-buffered saline (PBS) for 12 h, followed by treatment at a wavelength of 980 nm and a power of 1.0 W / cm². 2 Light processing for 3 minutes, followed by continuous processing for 12 hours; Subsequently, 10 μL of thiazolyl blue (MTT) was added to each well, and the mixture was incubated at 37°C for 4 h. Then, 100 μL of 10% sodium dodecyl sulfate (SDS) was added to each well, and the mixture was incubated at 37°C for 12 h. The absorbance (peak absorbance) of each well was measured at 570 nm using a microplate reader, and the absorbance at 650 nm (background absorbance) was subtracted. The cell viability under different treatments was then calculated. Specific experimental results are attached. Figure 13 As shown.

[0043] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A ruthenium-containing polymer, characterized in that, The ruthenium-containing polymer is obtained by Stille coupling polymerization of dibromohexacoordinate ruthenium complex, photoresponsive dibromo monomer, reactive oxygen species responsive dibromo monomer and ditin monomer under the catalysis of a catalyst. The catalyst includes a palladium-containing catalyst; The dibromohexacoordinate ruthenium complex has a ruthenium metal element at its center, and three dinitrogen-containing ligands coordinate around the ruthenium metal element to form a hexacoordinate ruthenium complex, wherein at least one nitrogen-containing ligand has at least two Br groups; The photoresponsive dibromo monomer has a conjugated structure and at least two Br groups; The reactive oxygen species-responsive dibromo monomer has chemical bonds that can be broken in response to reactive oxygen species and at least two Br groups; The bistin monomer has at least two trimethyltin groups.

2. The ruthenium-containing polymer according to claim 1, characterized in that, The catalyst comprises tris(o-methylphenyl)phosphine and tris(dibenzylacetone)dipalladium(O); Preferably, the molar ratio of tris(o-methylphenyl)phosphine to tris(dibenzylacetone)palladium(O) is (16-20):(4-5); Preferably, the ratio of the total molar amount of the dibromohexacoordinate ruthenium complex, the photoresponsive dibromo monomer, the reactive oxygen species-responsive dibromo monomer, and the ditin monomer to the total molar amount of the catalyst is (19-22):

1.

3. The ruthenium-containing polymer according to claim 1 or 2, characterized in that, The total molar amount of the dibromohexacoordinate ruthenium complex, the photoresponsive dibromo monomer, and the reactive oxygen species responsive dibromo monomer is in a molar ratio of 1:1 to that of the ditin monomer. Preferably, the molar ratio of the dibromohexacoordinate ruthenium complex, the photoresponsive dibromo monomer, and the reactive oxygen species responsive dibromo monomer is (0.5~1.5):(0.5~1.5):0.5; Preferably, the chemical bonds that are responsive to reactive oxygen species breaking include thioketone bonds or diselenylene bonds.

4. The ruthenium-containing polymer according to any one of claims 1-3, characterized in that, The dibromohexacoordinate ruthenium complex is selected from one of the following compounds: ； Preferably, the photoresponsive dibromo monomer is selected from one of the following compounds: 。 5. The ruthenium-containing polymer according to any one of claims 1-4, characterized in that, The bistin monomer is selected from one of the following compounds: ； Preferably, the reactive oxygen species-responsive dibromo monomer is selected from one of the following compounds: 。 6. The ruthenium-containing polymer according to any one of claims 1-5, characterized in that, The ruthenium-containing polymer comprises a structure as shown in any one of Formulas 1-30: ； Wherein, the molar ratio of x, y and z is (0.5~1.5):(0.5~1.5):0.5; Preferably, the molar ratio of x, y and z is 1:1:0.

5.

7. A method for preparing the ruthenium-containing polymer according to any one of claims 1-6, characterized in that, Includes the following steps: Stille coupling polymerization was carried out in a solvent with the addition of a catalyst using the aforementioned dibromohexacoordinate ruthenium complex, photoresponsive dibromo monomer, reactive oxygen species responsive dibromo monomer, and ditin monomer.

8. The method for preparing the polymer according to claim 7, characterized in that, The solvent includes toluene; Preferably, the Stille polymerization reaction is carried out under an inert gas atmosphere; Preferably, the reaction temperature of the Stille polymerization reaction is 90-110°C.

9. Use of the ruthenium-containing polymer according to any one of claims 1-6 or the ruthenium-containing polymer prepared by the preparation method according to claim 7 or 8 in the preparation of a medicament for treating tumors; Preferably, the drug for treating tumors includes drugs for photothermal therapy and / or photodynamic therapy of tumors.

10. A nanoparticle, characterized in that, The nanoparticles include: a) an amphiphilic carrier; b) a ruthenium-containing polymer as described in any one of claims 1-6 or a ruthenium-containing polymer prepared by the preparation method described in claim 7 or 8; Preferably, the amphiphilic carrier includes methoxy polyethylene glycol-distearate phosphatidylethanolamine, distearate phosphatidylethanolamine-diethylenetriaminepentaacetic acid, and methoxy poly(2-ethyl-2-oxazoline)-polylactic acid-hydroxyacetic acid copolymer.

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