Preparation and application of ROS (reactive oxygen species) response type nanoparticles containing thioketal bonds

Abstract

The invention relates to preparation and application of ROS (reactive oxygen species) responsive nanoparticles containing thioketal bonds, which can effectively solve the problems of poor biocompatibility, poor water solubility, uncontrollable release and the like of curcumin. The materials comprise curcumin, 4-carboxyphenylboronic acid, chitosan oligosaccharide and thioketal diacid. Chitosan oligosaccharide is modified by 4-carboxyphenylboronic acid, and then thioketal diacid is cross-linked to obtain the ROS responsive polymer. The polymer, curcumin and glucose oxidase are self-assembled in a solution to construct ROS-responsive nanoparticles. According to the nanoparticles prepared by the invention, due to the introduction of ROS-sensitive thioketal bonds and boric acid ester bonds, the controlled release of curcumin at a tumor part is realized under the stimulation of a tumor microenvironment. In addition, the encapsulated glucose oxidase can catalyze over-expressed glucose at tumor tissues to generate hydrogen peroxide, the ROS concentration of tumor cells is increased, the drug release efficiency is enhanced, and the treatment effect of the drug on breast cancer is effectively improved.

Description

Technical Field

[0001] The present invention belongs to the field of advanced nanocomposites and biomedical technologies, and specifically relates to the preparation and application of ROS-responsive nanoparticles containing thioacetal bonds. Background Art

[0002] As an important means of cancer treatment, chemotherapy plays an irreplaceable role in clinical practice. In recent years, natural products have received extensive attention in the research and development of anti-tumor drugs. Among them, curcumin is a hydrophobic polyphenolic compound extracted from turmeric rhizomes, which has significant antioxidant, anti-inflammatory and anti-tumor effects. Research shows that curcumin can induce apoptosis of tumor cells and inhibit their proliferation and metastasis by regulating multiple signaling pathways such as NF-κB, STAT3, and PI3K / Akt. However, curcumin has disadvantages such as poor water solubility and biological safety as an anti-cancer drug, and is easily metabolized and cleared rapidly in vivo, severely limiting its application in cancer treatment.

[0003] With the rapid development of nanotechnology, a variety of nano-drug delivery systems have been successfully developed and applied for the targeted delivery of curcumin to improve its biocompatibility and ensure its long circulation in vivo. However, the complex tumor microenvironment - including abnormal vascular systems, immunosuppressive cell populations, and special physicochemical properties (such as low pH value, low oxygen concentration, high reactive oxygen species concentration, etc.) severely limits the effective delivery and physiological activity of nano-drug-loaded particles. Therefore, the development of nano-drug-loaded particles that can rapidly respond to the tumor microenvironment remains a challenge. Smart-responsive polymers, as an emerging drug carrier, mainly encapsulate chemical drugs through self-assembly or chemical bonding, and control the release of drugs after specific stimuli to induce apoptosis and autophagy of tumor cells, thereby efficiently killing tumor cells and reducing drug side effects. Among them, reactive oxygen species (ROS)-responsive polymers are a typical type of nano-drug delivery carrier. According to different oxidation-sensitive moieties, they can be divided into those containing sulfur, selenium, tellurium, phenylboronic acid / ester, thioacetal, etc. At present, more and more ROS-responsive polymers have been used for drug delivery and controlled release, and significant achievements have been made in tumor treatment.

[0004] Currently, the polymers responsive to ROS mainly use chemically synthesized high-molecular materials, which generally have problems such as high cytotoxicity, poor biocompatibility, and difficult in vivo metabolism. In addition, the preparation process of synthetic high-molecular materials is complex and the cost is high, which seriously restricts their application and popularization in the field of drug delivery. Therefore, it has important research value to develop a ROS-responsive nanodrug delivery system based on natural high-molecular materials. As a cationic natural polysaccharide with good biocompatibility and low toxicity, chitosan oligosaccharide has been widely used as a non-viral vector for gene delivery. However, the existing ROS-responsive nanodrug carriers based on chitosan oligosaccharide still face technical bottlenecks, such as the crosslinking degree of the carrier is difficult to precisely control. If the crosslinking is incomplete, drug leakage is likely to occur during systemic circulation. When the crosslinking degree is too high, the ROS concentration in the tumor microenvironment is not sufficient to trigger the disassembly of the carrier, and the drug cannot be effectively released, resulting in an unsatisfactory therapeutic effect. Therefore, developing a chitosan oligosaccharide nanodrug carrier with controllable crosslinking degree and ROS responsiveness is of great significance for the precise targeted treatment of cancer with natural products.

[0005] Therefore, based on the above background, the applicant designs a ROS-responsive nanodrug-loaded particle based on dithioacetal bond and phenylboronic acid bond double-crosslinked chitosan oligosaccharide. Utilizing the cationicity of chitosan oligosaccharide to encapsulate negatively charged glucose oxidase, this enzyme can catalyze the glucose overexpressed at the tumor tissue to produce hydrogen peroxide, increase the ROS concentration in the tumor microenvironment, and trigger the cleavage of the dithioacetal bond to achieve precise and controllable drug release. This cascade amplification strategy effectively improves the accumulation and release efficiency of the drug at the tumor site and significantly enhances the therapeutic effect on tumors. Summary of the Invention

[0006] The primary object of the present invention is to overcome the deficiencies of the prior art and provide a preparation method of a ROS-responsive nanoparticle containing a dithioacetal bond. This method selects dithioacetal diacid as the ROS-responsive monomer to improve problems such as poor stability and low delivery efficiency of the nanoparticles. Secondly, phenylboronic acid is also used to modify chitosan oligosaccharide to make it a more stable nanocomposite, and at the same time polymerize with dithioacetal diacid to form a polymer, so that after forming nanoparticles, it has a stronger drug encapsulation ability and can be stably released in vivo. Finally, the polymer self-assembles to form micelles to encapsulate curcumin and glucose oxidase to prepare nanoparticles.

[0007] Another object of the present invention is to obtain a ROS-responsive nanoparticle containing a dithioacetal bond through the above preparation method. This nanoparticle has good biocompatibility, can effectively enhance the stable delivery of drugs, and shows important application prospects in the delivery of drugs for treating tumors with intelligent responsive drug carriers.

[0008] Another object of the present invention is to provide the application of the above-mentioned ROS-responsive nanoparticles containing thioacetal bonds, especially in the treatment of deep cancers such as breast cancer, liver cancer, and lung cancer after the intelligent response drug carrier encapsulates drugs.

[0009] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0010] A preparation method of ROS-responsive nanoparticles containing thioacetal bonds, comprising the following steps:

[0011] The first step, preparation of phenylboronic acid-grafted chitosan oligosaccharide: Dissolve 4-carboxyphenylboronic acid, N-hydroxysuccinimide (NHS), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) in dimethyl sulfoxide. After 30 minutes, dissolve chitosan oligosaccharide in distilled water and drop it into the above solution, and react at room temperature; after dialysis with distilled water, suction filtration, remove the solvent and unreacted monomers, and dry to obtain phenylboronic acid-grafted chitosan oligosaccharide (COS-CBA);

[0012] The second step, preparation of ROS-responsive monomer: Add 3-mercaptopropionic acid, acetone, and trifluoroacetic acid (TFA) to a reaction flask, stir and react at room temperature under nitrogen protection for 4 hours, and then transfer the reaction solution to an ice bath to quench the reaction. Filter to obtain the crude product, wash the crude product alternately with cold distilled water and n-hexane 3 times, and dry in vacuum at room temperature to obtain a white solid powder of thioacetal diacid, that is, the ROS-responsive monomer (TK);

[0013] The third step, synthesis of polymer: Dissolve the ROS-responsive monomer (TK), N-hydroxysuccinimide (NHS), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide obtained in step (2) in distilled water. After 30 minutes, add the phenylboronic acid-grafted chitosan oligosaccharide (COS-CBA) obtained in step (1) thereto. After the reaction is completed, dialyze in deionized water for 24 hours, and freeze-dry to obtain a polymer (COS-CBA-TK);

[0014] The fourth step, synthesis of ROS-responsive nanoparticles: Dissolve the polymer (COS-CBA-TK) obtained in step (3) in distilled water, dissolve curcumin in dimethyl sulfoxide, and dissolve glucose oxidase in distilled water. Slowly drop the two solutions into the polymer solution; react for 24 hours to prepare ROS-responsive nanoparticles.

[0015] The dosages of 4-carboxyphenylboronic acid, N-hydroxysuccinimide (NHS), 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and chitosan oligosaccharide in the first step are in a molar ratio of 1-5:1.32:1.32:1;

[0016] The dosage of distilled water described in Step 1 is calculated based on dissolving 400 - 500 mg of phenylboronic acid per 10 mL;

[0017] The dosage of dimethyl sulfoxide described in Step 1 is calculated based on dissolving 400 - 500 mg of chitosan oligosaccharide per 10 mL;

[0018] The reaction described in Step 1 is a magnetic stirring reaction at room temperature for 24 hours;

[0019] The dialysis condition of the distilled water described in Step 1 is dialysis for 1 - 5 days using a dialysis bag with a molecular weight cut-off of 500 - 1000 Da;

[0020] The dosages of monomer 3-mercaptopropionic acid, acetone, and trifluoroacetic acid (TFA) described in Step 2 are in a molar ratio of 1:5 - 30:0.5 - 3;

[0021] The dosage of acetone described in Step 2 is calculated based on adding 2 - 2.5 mL of 3-mercaptopropionic acid per 1 mL;

[0022] The reaction described in Step 2 is a magnetic stirring reaction at room temperature for 4 - 5 hours under N2 protection;

[0023] The dosages of phenylboronic acid grafted chitosan oligosaccharide (COS-CBA) and ROS-responsive monomer (TK) described in Step 3 are in a molar ratio of 1:1;

[0024] The dosage of distilled water described in Step 3 is calculated based on adding 200 - 300 mg of thioacetal dicarboxylic acid per 10 mL;

[0025] The condition for preparing the polymer in the reaction described in Step 3 is a magnetic stirring reaction at room temperature for 24 h;

[0026] The dialysis condition for preparing the polymer in the reaction described in Step 3 is dialysis for 1 - 5 days using a dialysis bag with a molecular weight cut-off of 500 - 2000 Da;

[0027] The dosages of each component described in Step 4 are used to prepare ROS-responsive nanoparticles according to the ratio of polymer (COS-CBA-TK):curcumin:glucose oxidase = 10 - 20:1:0.1 - 0.2;

[0028] The dosage of dimethyl sulfoxide described in Step 4 is calculated based on adding 10 mg of curcumin per 1 mL;

[0029] The dosage of distilled water described in Step 4 is calculated based on adding 100 mg of polymer per 10 mL;

[0030] The dosage of distilled water described in Step 4 is calculated based on adding 10 mg of glucose oxidase per 1 mL;

[0031] The conditions for preparing ROS-responsive nanoparticles in Step 4 are 15-35 °C, with magnetic stirring for 12-24 h.

[0032] The drying in Step 1 for preparing phenylboronic acid-grafted chitosan oligosaccharide (COS-CBA) and in Step (3) for preparing the polymer (COS-CBA-TK) is preferably freeze-drying.

[0033] The drying in Step 2 for preparing thioacetalized diacid monomer (TK) is preferably vacuum drying.

[0034] Unless otherwise specified, the reaction temperature in the present invention is room temperature. The preferred room temperature is 15-35 °C.

[0035] A ROS-responsive nanoparticle containing a thioacetal bond is obtained by the above preparation method.

[0036] The application of the above ROS-responsive nanoparticle containing a thioacetal bond in treating tumors.

[0037] The present invention has the following advantages and effects over the prior art:

[0038] (1) The present invention uses phenylboronic acid-grafted chitosan oligosaccharide as the core.

[0039] (2) The ROS-responsive nanoparticle containing a thioacetal bond prepared by the present invention has good biocompatibility and anti-tumor effect. Description of the Drawings

[0040] Figure 1 It is the synthesis route diagram of the material prepared in Example 1.

[0041] Figure 2 It is the 1 1H-NMR nuclear magnetic resonance characterization spectrum of chitosan oligosaccharide grafted with phenylboronic acid (COS-CBA) in Example 1.

[0042] Figure 3 It is the 1 1H-NMR nuclear magnetic resonance characterization spectrum of thioacetalized diacid monomer (TK) in Example 1.

[0043] Figure 4 It is the 1 1H-NMR nuclear magnetic resonance characterization spectrum of the polymer (COS-CBA-TK) in Example 1.

[0044] Figure 5 It is the FT-IR characterization diagram of the monomer and the polymer (COS-CBA-TK) in Example 1.

[0045] Figure 6 It is the nano-particle size diagram of curcumin nanoparticles in Example 1.

[0046] Figure 7 Zeta potential diagrams of different materials in Example 1;

[0047] Figure 8 Toxicity test of COS-CBA-TK-Cur-GOx against L929 cells in Example 4;

[0048] Figure 9 Toxicity test of COS-CBA-TK-Cur-GOx against 4T1 cells in Example 4;

[0049] Figure 10 Tumor inhibition rate of COS-CBA-TK-Cur-GOx against 4T1 mice in Example 5;

[0050] Figure 11 Tumor volume change curve of 4T1 mice in Example 5. Detailed implementation manners

[0051] The following further describes the present invention in detail with reference to the accompanying drawings and embodiments. However, the accompanying drawings and embodiments do not limit the technical solutions of the present invention. All changes or equivalent replacements made based on the teachings of the present invention fall within the protection scope of the present invention.

[0052] Example 1

[0053] The preparation method of ROS-responsive nanoparticles containing thioacetal bonds in this example includes the following steps:

[0054] (1) Chitosan modified phenylboronic acid: After activating phenylboronic acid (1.1 mmol, 182.5 mg) with EDC (1.32 mmol, 151.92 mg) and NHS (1.32 mmol, 253 mg) in DMSO for 30 min, weigh chitosan (1 mmol, 161.16 mg), dissolve it in distilled water and add it to the reaction. React at room temperature for 24 h. After the reaction is completed, transfer the mixture into a dialysis bag (cut-off molecular weight is 500), place it in ultrapure water for dialysis, change the ultrapure water every 4 h, and dialyze for 24 h in the dark throughout the process. After dialysis, perform freeze-drying to obtain a solid chitosan derivative (COS-CBA).

[0055] (2) Preparation of ROS monomer: Weigh 3-mercaptopropionic acid (55.0 mmol, 4.8 mL), acetone (25.0 mmol, 1.9 mL) and 50 μL trifluoroacetic acid (TFA) and add them into a 15 mL reaction flask. Stir and react at room temperature for 4 h under nitrogen protection, then transfer the reaction solution to an ice bath to quench the reaction. Then filter the mixture with a Buchner funnel to obtain a crude product, wash the crude product alternately with cold distilled water and n-hexane 3 times, and finally dry it under vacuum at room temperature to obtain a white solid powder thioacetal diacid (TK);

[0056] (3) Synthesis of polymer: Weigh 1 mmol (252 mg) of dithioacetal diacid, 1.2 mmol (186.3 mg) of EDC, and 1.2 mmol (230 mg) of NHS and add them to a 15 mL reaction flask. After adding 5 mL of purified water and activating for 30 min, weigh 1 mmol (268.3 mg) of chitosan derivative and add it to the reaction. After reacting at room temperature for 24 h, transfer the mixture into a dialysis bag (cut-off molecular weight is 500), dialyze for 24 h, and then freeze-dry the mixture to obtain the polymer (COS-CBA-TK).

[0057] (4) Synthesis of curcumin nanoparticles: Dissolve 2 mg of curcumin (Cur) in 200 μL of dimethyl sulfoxide, and at the same time dissolve 20 mg of the polymer obtained in step (3) in 20 mL of distilled water. Drop the curcumin solution into the polymer aqueous solution, and then continue to drop 200 μL of glucose oxidase solution (5 mg / mL) into the solution. Stir magnetically at room temperature for 24 h to prepare curcumin nanoparticles (COS-CBA-TK-Cur-GOx).

[0058] Example 2

[0059] The preparation method of ROS-responsive nanoparticles containing dithioacetal bonds in this example includes the following steps:

[0060] (1) Modification of chitosan with phenylboronic acid: After activating 2.2 mmol (365 mg) of phenylboronic acid, 1.32 mmol (151.92 mg) of EDC, and 1.32 mmol (253 mg) of NHS in DMSO for 30 min, weigh 1 mmol (161.16 mg) of chitosan, dissolve it in distilled water, and then add it to the reaction. React at room temperature for 24 h. After the reaction is completed, transfer the mixture into a dialysis bag (cut-off molecular weight is 500), place it in ultrapure water for dialysis, change the ultrapure water every 4 h, and dialyze for 24 h in the dark throughout the process. After dialysis, perform freeze-drying to obtain the solid chitosan derivative (COS-CBA).

[0061] Steps (2), (3), and (4) are the same as those in Example 1.

[0062] Example 3

[0063] The preparation method of ROS-responsive nanoparticles containing dithioacetal bonds in this example includes the following steps:

[0064] (1) Chitosan-modified phenylboronic acid: After activating phenylboronic acid (10 mmol, 1.66 g), EDC (2.64 mmol, 303.84 mg), and NHS (2.64 mmol, 506 mg) in DMSO for 30 min, weigh chitosan (2 mmol, 322.32 mg), dissolve it in distilled water, and then add it to the reaction. React at room temperature for 24 h. After the reaction is completed, transfer the mixture into a dialysis bag (cut-off molecular weight is 500), place it in ultrapure water for dialysis, change the ultrapure water every 4 h, and perform dialysis in the dark for 24 h. After dialysis, perform freeze-drying to obtain a solid chitosan derivative (COS-CBA).

[0065] (4) Synthesis of curcumin nanoparticles: Dissolve 2 mg of curcumin (Cur) in 200 μL of dimethyl sulfoxide, and at the same time dissolve 40 mg of the polymer obtained in step (3) in 20 mL of distilled water. Drop the curcumin solution into the aqueous polymer solution, and then continue to drop 200 μL of glucose oxidase solution (5 mg / mL) into the solution. React under magnetic stirring at room temperature for 24 h to prepare curcumin nanoparticles (COS-CBA-TK-Cur-GOx).

[0066] Step (2) is the same as in Example 1.

[0067] Example 4

[0068] CCK-8 experiment: Co-culture the nano-carriers of the thiosemicarbazone diacid (COS-CBA-TK) derivative of chitosan oligosaccharide prepared in Example 1 with different concentrations, the COS-CBA-TK-Cur-GOx nanoparticles after loading curcumin and glucose oxidase, and the free drug Cur, respectively, with tumor cells with elevated reactive oxygen species: 4T1 (mouse breast cancer cells) and normal cells: L929 (mouse fibroblasts) for 12 hours, and use the CCK-8 method to detect cell viability. The results show that compared with L929 normal cells, the reactive oxygen species-responsive COS-CBA-TK-Cur-GOx nano-drug has higher toxicity to 4T1 cells, and its selective anti-tumor effect is better than that of Cur.

[0069] Example 5

[0070] When the tumor size of 4T1 tumor-bearing mice reaches 100 mm 3When the time was right, COS-CBA-TK-Cur-GOx in Example 1 was intravenously injected into mice. The tumor volumes were measured on the 1st, 3rd, 5th, 7th, 9th, 11th, and 13th days respectively, and the tumor change trend was observed. Finally, an antitumor curve was plotted. According to formula (1), the antitumor rate was calculated to be 76.8% after 14 days of chemotherapy treatment. Where V represents the tumor volume of the treatment group, and Vc represents the tumor volume of the control group mice. Antitumor rate = (1 - V / Vc)·100% (1) In the in vivo treatment experiment, the inhibitory effects of each group on tumors were compared by recording the changes in tumor volume. The results showed that the efficacy of COS-CBA-TK-Cur-GOx was significant compared with the PBS group. This was because the increase in ROS in the tumor led to the cleavage of the dithioacetal bond, and the nanomicelles released curcumin, which had a significant inhibitory effect on the tumor.

[0071] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A method for preparing ROS-responsive nanoparticles containing thioacetal bonds, characterized in that: The following steps are involved: The first step is to prepare phenylboronic acid grafted chitosan oligosaccharide: 4-carboxyphenylboronic acid, N-hydroxysuccinimide (NHS), and 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) are dissolved in dimethyl sulfoxide, and after 30 minutes, chitosan oligosaccharide is dissolved in distilled water, and added dropwise to the above solution to react at room temperature; after dialysis with distilled water, suction filtration, removal of solvent and unreacted monomers, and drying, phenylboronic acid grafted chitosan oligosaccharide (COS-CBA) is obtained; Step 2: Preparation of ROS-responsive monomer: 3-mercaptopropionic acid, acetone and trifluoroacetic acid (TFA) were added to a reaction bottle, stirred at room temperature for 4 hours under nitrogen protection, and then the reaction solution was transferred to an ice bath to quench the reaction; the crude product was filtered, and the crude product was washed alternately with cold distilled water and n-hexane for 3 times, and dried under vacuum at room temperature to obtain a white solid powder of thioketal diacid, i.e., ROS-responsive monomer (TK); Step 3, synthesis of polymer: the ROS response monomer (TK), N-hydroxysuccinimide (NHS) and 1-ethyl-(3-dimethylaminopropyl) carbodiimide obtained in step 2 were dissolved in distilled water, and after 30 minutes, the phenylboronic acid grafted chitosan oligosaccharide (COS-CBA) obtained in step 1 was added thereto, the reaction was terminated, dialyzed in deionized water for 24 hours, and freeze-dried to obtain a polymer (COS-CBA-TK); The fourth step is the synthesis of ROS-responsive nanoparticles: the polymer (COS-CBA-TK) obtained in step 3 is dissolved in distilled water, curcumin is dissolved in dimethyl sulfoxide, and glucose oxidase is dissolved in distilled water, and the two solutions are slowly added dropwise to the polymer solution; the reaction is carried out for 24 hours to prepare ROS-responsive nanoparticles.

2. The method for preparing a ROS-responsive nanoparticle containing a thioacetal bond according to claim 1, characterized in that: The amount of 4-carboxyphenylboronic acid, N-hydroxysuccinimide (NHS), 1-ethyl-(3-dimethylaminopropyl)carbodiimide and chitosan oligosaccharide described in step 1 is calculated according to a molar ratio of 1 to 5:1.32:1.32:1; the amount of distilled water is calculated based on dissolving 400 to 500 mg of phenylboronic acid per 10 mL; the amount of dimethyl sulfoxide is calculated based on dissolving 400 to 500 mg of chitosan oligosaccharide per 10 mL.

3. The method for preparing a ROS-responsive nanoparticle containing a thioacetal bond according to claim 1, characterized in that: The reaction described in step 1 is a magnetic stirring reaction at room temperature for 24 hours; the distilled water dialysis condition is to use a 500-1000Da dialysis bag for 1-5 days.

4. The method for preparing a ROS-responsive nanoparticle containing a thioacetal bond according to claim 1, characterized in that: The monomers 3-mercaptopropionic acid, acetone and trifluoroacetic acid (TFA) described in step 2 are used in a molar ratio of 1:5-30:0.5-3; the amount of acetone is calculated by adding 2-2.5 mL of 3-mercaptopropionic acid per 1 mL; the reaction is carried out under N2 protection with magnetic stirring at room temperature for 4-5 hours.

5. The method for preparing a ROS-responsive nanoparticle containing a thioacetal bond according to claim 1, characterized in that: The amounts of phenylboronic acid grafted chitosan oligosaccharide (COS-CBA) and ROS response monomer (TK) described in step 3 are mixed in a molar ratio of 1:1; the amount of distilled water used is calculated by adding 200-300 mg of acetal dicarboxylic acid per 10 mL.

6. The method for preparing a ROS-responsive nanoparticle containing a thioacetal bond according to claim 1, characterized in that: The conditions for preparing the polymer by the reaction described in step 3 are 24 hours of magnetic stirring reaction at room temperature; and the dialysis conditions for preparing the polymer by the reaction are 1 to 5 days of dialysis using a 500 to 2000 Da dialysis bag.

7. The method for preparing a ROS-responsive nanoparticle containing a thioacetal bond according to claim 1, characterized in that: The amount of each component described in step 4 is calculated according to the ratio of polymer (COS-CBA-TK): curcumin: glucose oxidase = 10-20:1:0.1-0.2 to prepare ROS-responsive nanoparticles; the amount of dimethyl sulfoxide described in step 4 is calculated by adding 10 mg of curcumin per 1 mL; the amount of distilled water described in step 4 is calculated by adding 100 mg of polymer per 10 mL; the amount of distilled water described in step 4 is calculated by adding 10 mg of glucose oxidase per 1 mL.

8. The method for preparing a ROS-responsive nanoparticle containing a thioacetal bond according to claim 1, characterized in that: The reaction conditions for preparing ROS-responsive nanoparticles in step 4 are 15-35° C. and magnetic stirring for 12-24 hours.

9. A ROS-responsive nanoparticle containing a thioacetal bond, obtained according to the method for preparing a ROS-responsive nanoparticle containing a thioacetal bond according to any one of claims 1 to 8.

10. Use of ROS-responsive nanoparticles containing thioacetal bonds obtained by the method for preparing ROS-responsive nanoparticles containing thioacetal bonds according to any one of claims 1 to 8 in treating tumors.

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