GSH response type confinement aggregation gold nano-vesicle, preparation method thereof and application of GSH response type confinement aggregation gold nano-vesicle in radiosensitization
By modifying MnO2 with GSH-responsiveness on the surface of AuNPs and coating mesoporous silica, GSH-responsive limited-domain aggregate gold nanovesicles are formed, which solves the problem of limited radiosensitization effect of existing gold nanoparticles in vivo, and achieves a more efficient radiosensitization effect and a lower radiation dose.
Patent Information
- Application Number
- CN202510059343.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-15
- Publication Date
- 2025-05-27
AI Technical Summary
The existing gold nanoparticles have limited radiosensitization effects in the body and are difficult to dynamically control the assembly process, which leads to difficult to reduce the radiation dose of radiation therapy, tumor cells have strong radiation resistance, and X-rays damage adjacent normal tissue.
By optimizing the particle size of AuNPs and modifying GSH-responsive MnO2 on its surface, combined with mesoporous silica coating, GSH-responsive confined-domain aggregate gold nanovesicles, AuNP@MnO2 Ve@mSiO2, dynamic assembly and radiosensitization in vivo are achieved.
It enhances the radiation sensitization effect, reduces the dose of RT radiation, reduces the radiation resistance of tumor cells, and avoids X-ray damage to adjacent normal tissue.
Smart Images
Figure CN120037370A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biomedical technologies, and particularly relates to a preparation method of GSH-responsive confined aggregation gold nanovesicles and their application in radiosensitization.
Background Art
[0002] Self-assembled nanomaterials have great application potential as high-performance imaging and therapeutic agents for diagnosis and treatment. So far, the development of self-assembly technology in biomedical applications has mainly adopted two approaches. First, nanoparticles (NPs), as well-regulated entities, trigger self-assembly (pre-assembly) in vitro by external forces. However, the supramolecular structures and properties of pre-self-assembled nanomaterials usually change under complex physiological conditions, including uncontrollable dissociation, aggregation or transformation of the structure, accompanied by a weakening or even disappearance of the function. Second, using intrinsic biological processes to drive intelligent in vivo self-assembly (reassembly), in situ transforming the original structure in vivo, can prolong the residence time of the material at the diseased site, has obvious advantages in improving the treatment efficiency and reducing side effects, and can achieve precise cancer diagnosis and treatment. However, this endogenous in vivo self-assembly usually results in uncontrollable and disordered morphologies of the assembled bodies, which in turn leads to uncontrollable physicochemical properties of the assembled bodies in vivo. Therefore, in order to circumvent the limitations of these nanocomponents in vitro and in vivo, integrating in vitro and in vivo self-assembly strategies to make their advantages complementary is a potentially valuable method.
[0003] Many strategies have successfully precisely regulated self-assembled nanomaterials under in vivo physiological or pathological conditions. However, there are still some challenges, such as how to dynamically control the assembly or reassembly process and obtain direct evidence of the formation or transformation of nanostructures in vivo. Therefore, analytical methods or techniques should be developed to characterize the morphology of in vivo assembled bodies, real-time monitor and quantify the dynamic process of self-assembly, and locate the intrinsic stimulating factors.
[0004] Radiotherapy (RT) is a high-energy, highly penetrating ionizing radiation that can overcome the limited penetration of lasers into tissues and treat deep tumors. Gold nanoparticles (AuNPs) have strong X-ray attenuation, good biocompatibility and easily controllable sizes, and can be used as radiosensitizers to deposit radiation energy in tumors, which can reduce X-ray damage to adjacent normal tissues and improve the radiotherapy efficiency. However, after injecting AuNPs via the tail vein, the enrichment of AuNPs in tumors is limited, and the achieved radiosensitization effect is also limited, which is the main limitation of RT.
Summary of the Invention
[0005] The technical problem to be solved by the present invention is to provide a GSH-responsive confined aggregation gold nanovesicle, its preparation method and application in radiosensitization. By optimizing the particle size of AuNPs, especially by changing the particle spacing of AuNPs through a GSH-responsive confined aggregation strategy, enhancing its radiosensitization effect, thereby reducing the RT radiation dose, effectively reducing the radioresistance of tumor cells, and avoiding X-ray damage to adjacent normal tissues.
[0006] The present invention is implemented as follows:
[0007] A GSH-responsive confined aggregation gold nanovesicle, the gold nanovesicle is a mesoporous silica-coated vesicle AuNP@MnO 2 Ve@mSiO 2 , by in-situ forming GSH-responsive MnO on the surface of AuNPs 2 , obtaining AuNP@MnO 2 ; then modifying the surface of AuNP@MnO 2 with phosphoric acid-polystyrene block copolymer P-PS; then performing self-assembly on it to obtain the plasmonic gold nanovesicle AuNP@MnO 2 Ve; finally coating mesoporous silica on the surface of AuNP@MnO 2 Ve for modification and stabilization, and finally obtaining the GSH-responsive confined aggregation gold nanovesicle AuNP@MnO 2 Ve@mSiO 2 .
[0008] Furthermore, a preparation method of a GSH-responsive confined aggregation gold nanovesicle, the method steps are as follows:
[0009] Step 1, synthesis of AuNP@MnO 2 nanoparticles:
[0010] Mix the AuNPs solution with KMnO 4 under stirring, and slowly drop the ascorbic acid L-AA aqueous solution into the above mixed solution; after the reaction is completed, collect the obtained AuNP@MnO 2 nanoparticles by centrifugation;
[0011] Step 2, preparation of AuNP@MnO 2 Ve:
[0012] Add SH-PEG and phosphoric acid-polystyrene to the dichloromethane containing AuNP@MnO 2 nanoparticles, after the mixture reacts, collect the product by centrifugation to remove the free polymer, and obtain the amphiphilic AuNP@MnO 2 @P-PS NPs;
[0013] Disperse AuNP@MnO 2 @P-PS NPs in dichloromethane, and then add 5% aqueous solution of polyvinyl alcohol (PVA) for ultrasonic emulsification; at room temperature, dichloromethane completely evaporates to form AuNP@MnO 2 Ve; then wash the obtained AuNP@MnO 2 Ve with deionized water to remove the excess PVA, and AuNP@MnO 2 Ve is obtained.
[0014] Step 3: Synthesis of AuNP@MnO 2 Ve@mSiO 2 :
[0015] Add sodium hydroxide solution to cetyltrimethylammonium bromide (CTAB) solution, and then add AuNP@MnO 2 Ve and stir; then add 5% methanol solution of tetraethyl orthosilicate (TEOS) and 5% 3-aminopropyltriethoxysilane (APTES) to the solution, and add them three times every 30 min at 33 °C; after the reaction is completed, first centrifuge the product, and then disperse it in ethanol 2 - 3 times; after ultrasonic treatment for 0.5 h, centrifuge to obtain mesoporous silica-coated vesicles AuNP@MnO 2 Ve@mSiO 2 .
[0016] Furthermore, in step 1, the particle size of AuNPs is 8 - 20 nm; the thickness of MnO 2 in the middle layer of the gold nanovesicles is between 2 - 8 nm; the thickness of the surface-coated mSiO 2 layer is 0.5 - 10 nm.
[0017] Furthermore, in step 1, the molar ratio of each reactant is AuNPs: KMnO 4 : L-AA = 5 - 10: 0.1 - 1: 0.01 - 10.
[0018] Furthermore, in step 2, the mass ratio of each reactant is AuNP@MnO 2 nanoparticles: SH-PEG: phosphoric acid-polystyrene = 2 - 10: 0.1 - 1: 0.5 - 5.
[0019] Furthermore, in step 3, the amount of each reactant is AuNP@MnO 2 Ve: CTAB: TEOS: APTES = 2 - 10: 0.3 - 2: 0.1 - 4: 0.1 - 2.
[0020] Furthermore, the synthesis steps of AuNPs gold nanoparticles are as follows:
[0021] Chloroauric acid solution was added to ultrapure water, and the mixed solution was refluxed at 100 ± 10 °C for 8 ± 2 min; then sodium citrate solution was quickly added to the mixed solution, and the reaction was carried out for 10 ± 2 min; finally, a blood-red AuNPs solution was obtained; after cooling to room temperature, it was stored in a 4 °C refrigerator for standby.
[0022] Furthermore, the application of the GSH-responsive confined aggregation gold nanovesicles in the preparation of a radiotherapy sensitizer.
[0023] The present invention has the following advantages:
[0024] The present invention develops a GSH-responsive gold nanocomposite AuNP@MnO 2 Ve@mSiO 2 that can be realized at the in vivo level. Through an in vitro pre-assembly strategy and then an in vivo re-assembly process, the radiotherapy sensitization effect is further enhanced. Specifically, the present invention modifies MnO with GSH responsiveness on AuNPs 2 to obtain AuNP@MnO 2 ; then the surface of AuNP@MnO 2 is modified with phosphoric acid-polystyrene block copolymer P-PS; then it is self-assembled to obtain plasmonic gold nanovesicles AuNP@MnO 2 Ve; finally, mesoporous silica is coated on the surface of AuNP@MnO 2 Ve for surface modification and stabilization, and finally the GSH-responsive confined aggregation gold nanovesicles AuNP@MnO 2 Ve@mSiO 2 are obtained. That is, under GSH conditions, the distance between AuNP@MnO 2 inside the vesicles of the gold nanovesicles of the present invention is reduced, realizing GSH-responsive confined aggregation and enhancing the radiotherapy sensitization effect.
[0025] In summary, the present invention optimizes the particle size of AuNPs, especially changes the particle spacing of AuNPs through the GSH-responsive confined aggregation strategy, enhances its radiotherapy sensitization effect, thereby reducing the RT radiation dose, effectively reducing the radioresistance of tumor cells, and avoiding X-ray damage to adjacent normal tissues.
Description of the Drawings
[0026] The present invention will be further described below with reference to the accompanying drawings in conjunction with the embodiments.
[0027] Figure 1 It is the transmission electron microscope TEM image of AuNPs prepared in the embodiment of the present invention.
[0028] Figure 2 It is AuNP@MnO prepared in the embodiment of the present invention2 TEM image.
[0029] Figure 3 AuNP@MnO prepared in the embodiment of the present invention 2 Energy-dispersive X-ray spectroscopy (EDS) elemental distribution map of NPs.
[0030] Figure 4 AuNP@MnO prepared in the embodiment of the present invention 2 TEM image of Ve.
[0031] Figure 5 AuNP@MnO prepared in the embodiment of the present invention 2 Ve@mSiO 2 TEM image.
[0032] Figure 6 AuNP@MnO after stimulation with 1 mM GSH in the embodiment of the present invention 2 Ve@mSiO 2 TEM image.
[0033] Figure 7 ESR spectrum for identifying hydroxyl radicals generated by the material prepared by X-ray irradiation in the embodiment of the present invention.
Detailed Implementation Modes
[0034] The following will combine the attached Figures 1-7 drawings and specific implementation modes to clearly and completely describe the technical solutions of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention. For those not specified in the embodiments, they shall be carried out according to conventional conditions or conditions recommended by the manufacturer. For reagents or instruments not specified by the manufacturer, they are all conventional products that can be obtained through commercial purchase.
[0035] Embodiment
[0036] 1 Preparation steps
[0037] 1.1 Synthesis of phosphoric acid-polystyrene, the specific steps are as follows:
[0038] Step A: Synthesis of initiator. 770 mg (1 eq) of dimethyl 2-hydroxyethylphosphonate was dissolved in 20 mL of dichloromethane, and triethylamine (3 eq) was added. The mixed solution was stirred in an ice-water bath for 30 min to cool down the reaction system. 2-Bromo-2-methylpropionyl bromide (1.2 eq) was dissolved in 5 mL of dichloromethane and added dropwise to the above mixed solution at a rate of one to two drops per second; then, after reacting in the ice-water bath for 1 h, the temperature was raised to room temperature and the reaction was carried out for 8 h. After the reaction was completed, the obtained mixed solution was concentrated to 5 mL, then 15 mL of ethyl acetate was added, and then the mixed solution was washed three times with saturated sodium bicarbonate solution and deionized water in turn. The organic phase of the mixed solution was collected, then anhydrous sodium sulfate was added to remove water, and the excess solvent was removed by rotary evaporation to obtain a viscous yellowish-brown liquid.
[0039] Step B: Synthesis of ATRP polymer. 1 g of styrene monomer and 28 μL of N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA) were dissolved in 3 mL of anisole, and then 30.3 mg of the above initiator was added. After the mixed solution was degassed for 30 min, 17 mg of copper(I) bromide was weighed and added to the mixed solution, and degassing was continued for 10 min (at this time, the color of the mixed solution was green). The mixed solution was placed in an oil bath at 105 °C and reacted for 12 h (the color of the solution changed to yellow after 30 min, indicating that the reaction occurred). After the reaction was completed, 5 mL of dichloromethane was added for dilution, and copper ions were removed using a silica gel column. The silica gel column was rinsed with dichloromethane, and the product was collected and concentrated by rotary evaporation. The concentrated solution was dropped into diethyl ether, and the precipitated white solid was collected and dried.
[0040] Step C: Demethylation synthesis of phosphate ester. Weigh ATRP polymer (1 eq) and dissolve it in 10 mL of dichloromethane. Trimethylsilyl bromide (5 - 10 eq) was added with stirring, and after reacting for 12 h, 5 mL of methanol was added and the reaction was continued for 12 h. The mixed solution was concentrated by rotary evaporation (the final volume was about 8 mL). Then, the mixed solution was dropped into diethyl ether, and the precipitated white solid was collected and dried.
[0041] 1.2 Synthesis of AuNPs gold nanoparticles
[0042] Chloroauric acid solution (1 mL, 20 mg mL -1 ) was added to 200 mL of ultrapure water, and the mixed solution was refluxed at about 100 °C for 8 min; then, 5 mL of sodium citrate solution containing 12 mg mL -1 was quickly added to the mixed solution, and the reaction was carried out for 10 min; finally, a blood-red 13 nm AuNPs solution was obtained. After cooling to room temperature, it was stored in a refrigerator at 4 °C for standby.
[0043] 1.3 Synthesis of AuNP@MnO 2 nanoparticles
[0044] Mix the AuNPs solution (0.5 mg mL -1 , 100 mL) with 42 mg KMnO 4 under stirring. After 5 min, slowly add 1 mL of 50 mg mL -1 aqueous solution of ascorbic acid (L-AA) into the above mixed solution. During the reaction process, the color of the solution changes from purple-red to yellow-brown and finally to black. Collect the obtained AuNP@MnO 2 nanoparticles by centrifugation.
[0045] 1.4 Preparation of AuNP@MnO 2 Ve
[0046] Add 4 mg of SH-PEG and 8 mg of phosphoric acid-polystyrene to 10 mL of dichloromethane containing AuNP@MnO 2 NPs (2 mg mL -1 ). After the mixture reacts for 8 h, collect the product by centrifugation (15,000×g, 20 min) to remove free polymers, and obtain amphiphilic AuNP@MnO 2 @P-PS NPs.
[0047] Prepare AuNP@MnO 2 Ve by the oil-in-water emulsion method: Disperse 5 mg of AuNP@MnO 2 @P-PS NPs in 200 μL of dichloromethane, and then add 5 mL of 5% polyvinyl alcohol PVA (Mw: 9000 - 10000) aqueous solution for ultrasonic emulsification. At room temperature, dichloromethane completely evaporates to form AuNP@MnO 2 Ve. Finally, wash the obtained AuNP@MnO 2 Ve three times with deionized water to remove excess PVA.
[0048] 1.5 Synthesis of AuNP@MnO 2 Ve@mSiO 2
[0049] Add 200 μL of 0.1 M sodium hydroxide (NaOH) solution to the cetyltrimethylammonium bromide (CTAB) solution, and add AuNP@MnO 2 Ve and stir. Add 120 μL of 5% methanol tetraethoxysilane (TEOS) and 48 μL of 5% APTES (APTES) to the solution, and add them three times every 30 min at 33 °C. After reacting for 48 h, centrifuge the product at 7000 rpm for 10 min, and then disperse it twice in ethanol (2 mg / mL). After ultrasonic treatment for 0.5 h, centrifuge to obtain AuNP@MnO coated with mesoporous silica2 Ve@mSiO 2 。
[0050] 2 Experimental Results
[0051] First, 10 nm AuNP was synthesized by the sodium citrate reduction method (as Figure 1 shown). Subsequently, through the in-situ reduction method of KMnO 4 , MnO 2 was coated on the outer surface of AuNPs to obtain AuNP@MnO 2 . As Figure 2 shown by the TEM image of AuNP@MnO 2 , it has a core-shell structure with a particle size of about 13 nm, where the thickness of the MnO 2 layer is about 3 nm (the thickness of the MnO 2 layer can be controlled by adjusting the initial dosages of the reducing agent L-AA and KMnO 4 or the reaction time). As Figure 3 shown, the STEM-Mapping elemental distribution analysis results of AuNP@MnO 2 nanoparticles further confirmed the MnO 2 layer coated on its surface.
[0052] Next, AuNP@MnO 2 was surface-modified with P-PS to obtain amphiphilic AuNP@MnO 2 @P-PS, and then AuNP@MnO 2 Ve was prepared by the ultrasonic emulsification method (as Figure 4 shown). Then, mesoporous silica was coated on the surface of AuNP@MnO 2 Ve to obtain AuNP@MnO 2 Ve@mSiO 2 . mSiO 2 makes AuNP@MnO 2 Ve@mSiO 2 have good stability. By observing the size and internal microstructure of AuNP@MnO 2 Ve@mSiO 2 vesicles through TEM, the results showed that AuNP@MnO 2 Ve@mSiO 2 has a typical nanovesicle structure with an average diameter of 140 nm (as Figure 5 shown). In addition, AuNP@MnO 2 NPs are evenly distributed in the vesicles, and the gap between them is about 8 - 10 nm, which is due to MnO 2caused by the barrier effect of the layer. In addition, an outer layer structure with lower electron density was observed in the AuNP@MnO 2 Ve@mSiO 2 vesicles, indicating that the mSiO 2 coating was uniformly deposited on the outermost layer of the vesicles.
[0053] As Figure 6 shown, when AuNP@MnO 2 Ve@mSiO 2 was incubated with 1 mM GSH, the AuNPs inside gradually underwent confined aggregation over time. This is because the mSiO 2 coated on the surface of the AuNP@MnO 2 Ve allowed GSH to freely enter and exit the vesicles. Therefore, the MnO 2 layer coated on the surface of the AuNP was etched into Mn 2+ by the action of GSH. The distance between the AuNP@MnO 2 NPs in the vesicles gradually decreased from the original 8 nm to close contact, ultimately leading to the aggregation of AuNP@MnO 2 NPs in the vesicles into a more compact entity.
[0054] To study the difference in the radiosensitizing effect of the vesicles before and after GSH treatment, the solutions of the dispersed materials, AuNPs, AuNP@MnO 2 Ve and AuNP@MnO 2 Ve@mSiO 2 were mixed with 1 mM GSH solution, irradiated with X-rays after incubation for 4 h, and the generated hydroxyl radicals (·OH, an indicator of radiosensitization) were measured using electron spin resonance spectroscopy (ESR). The results are as Figure 7 shown. The results showed that the ESR signal of AuNP@MnO 2 Ve@mSiO 2 significantly increased after GSH treatment. This is because Au-based materials generate ·OH through the transfer of X-ray energy to produce Auger electrons and Compton scattering. Under the stimulation of GSH, the AuNP@MnO 2 Ve@mSiO 2 in the AuNP@MnO 2 NPs gradually underwent confined aggregation, enhancing the radiosensitization effect and generating more ·OH. These results indicate that the AuNP@MnO 2 Ve@mSiO 2 in the AuNP@MnO 2 NPs underwent confined aggregation under the stimulation of GSH, forming a more compact structure, thereby producing a radiosensitizing effect.
[0055] In summary, the present invention has developed a GSH-responsive gold nanocomposite assembly AuNP@MnO 2 Ve@mSiO 2 that can be realized at the in-vivo level. Through an in-vitro pre-assembly strategy and then an in-vivo re-assembly process, the radiosensitization effect is further enhanced. Specifically, the present invention modifies MnO with GSH responsiveness on AuNPs 2 to obtain AuNP@MnO 2 ; then, a phosphoric acid-polystyrene block copolymer P-PS is modified on the surface of AuNP@MnO 2 ; then it is self-assembled to obtain the plasmonic gold nanovesicle AuNP@MnO 2 Ve; finally, mesoporous silica is coated on the surface of AuNP@MnO 2 Ve for surface modification and stabilization, and finally the GSH-responsive confined aggregation gold nanovesicle AuNP@MnO 2 Ve@mSiO 2 is obtained. That is, under GSH conditions, the distance between AuNP@MnO2 in the nanovesicle of the present invention is reduced, realizing GSH-responsive confined aggregation and enhancing the radiosensitization effect.
[0056] In short, the present invention optimizes the particle size of AuNPs, especially changes the particle spacing of AuNPs through the GSH-responsive confined aggregation strategy, enhances its radiosensitization effect, thereby reducing the RT radiation dose, effectively reducing the radioresistance of tumor cells, and avoiding X-ray damage to adjacent normal tissues.
[0057] Although the specific embodiments of the present invention have been described above, those skilled in the art should understand that the specific embodiments we described are illustrative rather than used to limit the scope of the present invention. Equivalent modifications and variations made by those skilled in the art in accordance with the spirit of the present invention should be covered by the scope protected by the claims of the present invention.
Claims
1. A GSH-responsive confined aggregation gold nanovesicle, characterized in that: The gold nanovesicles are coated with mesoporous silica to form vesicles AuNP@MnO2 Ve@mSiO2, and MnO2 with GSH responsiveness is formed in situ on the surface of AuNPs to obtain AuNP@MnO2; then, the surface of AuNP@MnO2 is modified with phosphoric acid-polystyrene block copolymer P-PS; then, it is self-assembled to obtain plasma gold nanovesicles AuNP@MnO2 Ve; finally, the surface of AuNP@MnO2 Ve is coated with mesoporous silica for modification and stabilization, and finally, GSH responsive confined aggregated gold nanovesicles AuNP@MnO2 Ve@mSiO2 are obtained.
2. A method for preparing GSH-responsive confined aggregated gold nanovesicles, characterized in that: The method steps are as follows: Step 1: Synthesis of AuNP@MnO2 nanoparticles: The AuNPs solution and KMnO4 were mixed under stirring, and the ascorbic acid L-AA aqueous solution was slowly dripped into the mixed solution; after the reaction was completed, the obtained AuNP@MnO2 nanoparticles were collected by centrifugation; Step 2: Preparation of AuNP@MnO2 Ve: SH-PEG and phosphoric acid-polystyrene were added to dichloromethane containing AuNP@MnO2 nanoparticles. After the mixture reacted, the product was collected by centrifugation to remove free polymers, thereby obtaining amphiphilic AuNP@MnO2@P-PS NPs. AuNP@MnO2@P-PS NPs were dispersed in dichloromethane, and then 5% polyvinyl alcohol (PVA) aqueous solution was added for ultrasonic emulsification; at room temperature, dichloromethane was completely evaporated to form AuNP@MnO2Ve; the obtained AuNP@MnO2 Ve was then washed with deionized water to remove excess PVA, thus obtaining AuNP@MnO2 Ve; Step 3, Synthesis of AuNP@MnO2Ve@mSiO2: Sodium hydroxide solution was added to hexadecyltrimethylammonium bromide (CTAB) solution, and then AuNP@MnO2 Ve was added and stirred; then 5% methanol tetraethoxysilane (TEOS) and 5% APTES were added to the solution at 33°C, three times every 30 minutes; after the reaction was completed, the product was first centrifuged and then dispersed in ethanol for 2 to 3 times; after ultrasonication for 0.5 hours, the product was centrifuged to obtain mesoporous silica-coated vesicles AuNP@MnO2 Ve@mSiO2.
3. The method for preparing a GSH-responsive confined aggregated gold nanovesicle according to claim 2, characterized in that: The particle size of AuNPs in step 1 is 8 to 20 nm; the thickness of MnO2 in the middle layer of the gold nanocapsule is between 2 and 8 nm; and the thickness of the surface-coated mSiO2 layer is 0.5 to 10 nm.
4. The method for preparing a GSH-responsive confined aggregated gold nanovesicle according to claim 2, characterized in that: The molar ratio of the reactants in step 1 is AuNPs:KMnO4:L-AA=5-10:0.1-1:0.01-10.
5. The method for preparing a GSH-responsive confined aggregation gold nanovesicle according to claim 2, characterized in that: The mass ratio of the reactants in step 2 is AuNP@MnO2 nanoparticles: SH-PEG: phosphoric acid-polystyrene = 2-10: 0.1-1: 0.5-5.
6. The method for preparing a GSH-responsive confined aggregation gold nanovesicle according to claim 2, characterized in that: The amount of each reactant in step 3 is AuNP@MnO2 Ve: CTAB: TEOS: APTES = 2-10: 0.3-2: 0.1-4: 0.1-2.
7. The method for preparing a GSH-responsive confined aggregation gold nanovesicle according to claim 2, characterized in that: The synthesis steps of AuNPs gold nanoparticles are as follows: Chloroauric acid solution was added to ultrapure water, and the mixed solution was refluxed at 100±10°C for 8±2 min; then sodium citrate solution was quickly added to the mixed solution, and the mixture was reacted for 10±2 min; finally, a blood-red AuNPs solution was obtained; after cooling to room temperature, the solution was stored in a 4°C refrigerator for later use.
8. Use of the GSH-responsive confined aggregated gold nanovesicles according to claim 1 in the preparation of a radiotherapy sensitizer.