Self-supply hydrogen peroxide composite nanoparticle and preparation method and application thereof

Abstract

The invention discloses a self-supply hydrogen peroxide composite nanoparticle as well as a preparation method and application thereof, and relates to the technical field of biological medicines, and the self-supply hydrogen peroxide composite nanoparticle is a CA (ZIF) ZIF-8 / MnO2 nanoparticle which takes ZIF-8 as a carrier, carries chlorogenic acid CA in situ to form a CA (ZIF) ZIF-8 nanoparticle, and is coated with a MnO2 shell layer outside, and is recorded as a CZM nanoparticle. The CA-ZIF-8 nano particles are prepared through an in-situ loading method, the problems that CA is poor in water solubility and easy to degrade can be remarkably solved, the CZM nano particles coated with a MnO2 uniform shell layer are prepared through reaction regulation of the CA and the ZIF-8 on KMnO4, the autoxidation characteristic of the CA is effectively utilized, continuous H2O2 reactant supply is provided for CDT reaction, excessive antioxidant substances GSH in tumor cells are consumed at the same time, and the tumor cells are effectively protected. The aim of improving CDT treatment on cancers is fulfilled. According to the nanoparticles, a sequence of firstly consuming GSH and then generating free radicals is effectively formed, and the synergistic anti-tumor effect of MnO2 and CA is effectively improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, and particularly relates to a self-supplying hydrogen peroxide composite nanoparticle, a preparation method and application thereof. BACKGROUND

[0002] Chemodynamic therapy (CDT) is a new cancer treatment method, which uses endogenous hydrogen peroxide (H2O2) in the tumor to produce the most destructive active oxygen species, hydroxyl radicals (•OH), under the mediation of Fenton or Fenton-like reaction of transition metal ions (such as Fe 2+ , Cu + , Mn 2+ , etc.), so as to achieve the effect of killing tumor cells. Compared with traditional treatment methods, CDT has higher tumor selectivity, spatiotemporal controllability, minimally invasive and lower systemic toxicity. However, the development of CDT therapy still faces many challenges, and the overexpression of glutathione (GSH) is one of the main obstacles. As a key component of the powerful ROS scavenging system, the GSH level in cancer cells is up-regulated due to the increased ROS level caused by abnormal proliferation and enhanced cell respiration. Although this regulation helps to maintain the redox homeostasis, it also leads to the rapid consumption of •OH before it exerts its cytotoxic effect, thereby enhancing the resistance of cancer cells to oxidative stress and reducing the efficacy of CDT.

[0003] In recent years, manganese dioxide (MnO2) has attracted much attention as a promising CDT nanoplatform material. This material mainly exerts multiple anti-tumor effects through the following mechanisms: first, the MnO2 nanostructure has unique GSH-responsive redox activity, which can be specifically degraded to manganese ions (Mn 2+ ) by the overexpressed GSH in tumor cells, and Mn 2+ has excellent Fenton-like catalytic ability, which can efficiently catalyze the conversion of endogenous H2O2 to •OH. Second, it can also simultaneously consume excess antioxidant GSH in tumor cells, significantly reducing the clearance rate of •OH, and achieving self-enhanced CDT by self-consumption of GSH.

[0004] Although the concentration of hydrogen peroxide (H2O2) in the tumor microenvironment is significantly higher than that in normal tissues, the endogenous H2O2 is still insufficient to produce sufficient •OH to achieve the ideal therapeutic effect. The limited content of H2O2 seriously restricts the efficacy of CDT, which has become another obstacle faced by CDT. Developing a nanoplatform that can self-supply H2O2 and achieve self-enhanced function by self-consumption of GSH to improve the efficacy of CDT has become a key scientific problem that needs to be solved urgently. SUMMARY

[0005] In view of the bottleneck of insufficient endogenous H2O2 in CDT treatment, the application aims to provide a self-supplying hydrogen peroxide composite nanoparticle. A small molecule organic compound, chlorogenic acid (CA), is used to efficiently convert high-concentration superoxide anions in tumor cells into H2O2, providing a continuous supply of reactants for CDT reaction, and combining with MnO2 to self-consume GSH, thereby realizing CDT treatment with self-supplying H2O2 and self-consuming GSH.

[0006] Another object of the application is to provide a preparation method of the self-supplying hydrogen peroxide composite nanoparticle. The method effectively solves the problems of poor water solubility and easy degradation of chlorogenic acid, poor uniformity of MnO2 coating, and poor matching of the processes of self-supplying H2O2 and self-consuming GSH, thereby resulting in poor synergistic effect.

[0007] The object of the application is achieved by the following technical solutions: A self-supplying hydrogen peroxide composite nanoparticle, characterized in that the composite nanoparticle is a CA@ZIF-8 / MnO2 nanoparticle with ZIF-8 as a carrier, in-situ loading of chlorogenic acid CA to form a CA@ZIF-8 nanoparticle, and coating of a MnO2 shell on the outside, denoted as CZM nanoparticle.

[0008] Further, the CA@ZIF-8 / MnO2 nanoparticle is prepared by dissolving zinc nitrate hexahydrate in deionized water to form a zinc nitrate solution, dissolving 2-methylimidazole in methanol to form solution I, dissolving chlorogenic acid CA in DMF to form solution II, adding the zinc nitrate solution to solution I, stirring for 5-10 min, then continuously adding solution II and stirring until the solution turns milky white, and continuously stirring for 3-5 min to obtain a CA@ZIF-8 nanoparticle solution, denoted as CZ solution.

[0009] Further, in the zinc nitrate solution, the mass-volume ratio of zinc nitrate hexahydrate to deionized water is 28-32 mg:1 mL.

[0010] Further, in the solution I, the mass-volume ratio of 2-methylimidazole to methanol is 35-38 mg:1 mL.

[0011] Further, in the solution II, the mass-volume ratio of CA to DMF is 18-22 mg:1 mL.

[0012] Further, the volume ratio of the zinc nitrate solution, solution I, and solution II is 0.45-0.55:0.8-1.2:0.1.

[0013] Further, the CZM nanoparticles are prepared by adding KMnO4 aqueous solution into the CZ solution for reaction, centrifugal treatment after the reaction is completed, dialysis of the centrifugal supernatant for 48 h, and freeze-drying of the precipitate.

[0014] Further, the concentration of the KMnO4 aqueous solution is 48-52 mg / L, and the volume ratio of the KMnO4 aqueous solution to the CZ solution is 1:7-9.

[0015] A preparation method of self-supply hydrogen peroxide composite nanoparticles, characterized by comprising the steps of preparing CA@ZIF-8 nanoparticles and coating MnO2, wherein the CA@ZIF-8 nanoparticles are prepared by dissolving zinc nitrate hexahydrate in deionized water to form a zinc nitrate solution, dissolving 2-methylimidazole in methanol to form a solution I, dissolving chlorogenic acid CA in DMF to form a solution II, adding the zinc nitrate solution into the solution I, stirring for 5-10 min, continuously adding the solution II and stirring until the solution appears milky white, and continuously stirring for 3-5 min to obtain a CA@ZIF-8 nanoparticle solution, which is denoted as a CZ solution.

[0016] Further, in the zinc nitrate solution, the mass-volume ratio of zinc nitrate hexahydrate to deionized water is 28-32 mg:1 mL.

[0017] Further, in the solution I, the mass-volume ratio of 2-methylimidazole to methanol is 35-38 mg:1 mL.

[0018] Further, in the solution II, the mass-volume ratio of CA to DMF is 18-22 mg:1 mL.

[0019] Further, the volume ratio of the zinc nitrate solution, the solution I and the solution II is 0.45-0.55:0.8-1.2:0.1.

[0020] Further, the coating of MnO2 is achieved by adding KMnO4 aqueous solution dropwise into the above CZ solution under stirring, continuously stirring at a speed of 500-700 rpm at room temperature for 25-35 min to obtain a brownish yellow solution, centrifuging the solution at a speed of 10000-13000 rpm for 8-12 min after the reaction is completed, dialyzing the centrifugal supernatant for 48 h, and freeze-drying the precipitate.

[0021] Further, the concentration of the KMnO4 aqueous solution is 48-52 mg / L, and the volume ratio of the KMnO4 aqueous solution to the CZ solution is 1:7-9.

[0022] It is found in the loading of CA that CA has poor water solubility and is prone to degradation, and the loading efficiency in ZIF-8 is low, resulting in an unsatisfactory self-supply of H2O2.

[0023] Secondly, the loading of chlorogenic acid on the surface of ZIF-8 can significantly affect the coating effect of MnO2. If the coating effect of MnO2 is not good, or the process of MnO2 consuming GSH and CA to generate free radicals does not match, it will lead to the free radicals generated by CA being cleared by GSH, resulting in a decrease in the synergistic effect.

[0024] In the in-situ loading process, the solution II is added in the middle of the preparation of ZIF-8, and CA is added when the ZIF-8 crystal nucleus is initially formed. This not only realizes the in-situ loading of CA, but also reduces the degradation of CA, improves the loading efficiency of CA in ZIF-8, adjusts the distribution of CA in ZIF-8, and makes a small amount of CA adhere to the periphery of ZIF-8 after in-situ loading, forming a weak reducing environment. In the subsequent coating process of MnO2, the reduction rate of KMnO4 to generate MnO2 is adjusted, and the deposition uniformity of MnO2 is improved. In addition, the method of in-situ loading can wrap CA mainly inside ZIF-8 and uniformly wrap MnO2 shell layer, rely on ZIF-8 to degrade synchronously with MnO2 shell layer in acidic tumor microenvironment, and control the release of CA. The order of consuming GSH and generating free radicals is formed, and the free radicals generated by CA are inhibited from being cleared by GSH which has not been consumed in time, so as to improve the synergistic antitumor effect of MnO2 and CA.

[0025] Most specifically, a preparation method of a self-supplying hydrogen peroxide composite nanoparticle, characterized in that it comprises the following steps: S1. Preparation of CA@ZIF-8 nanoparticle 75 mg of zinc nitrate hexahydrate is dissolved in 2.5 mL of deionized water to form a zinc nitrate solution, 165 mg of 2-methylimidazole is dissolved in 5 mL of methanol to form solution I, and 10 mg of CA is dissolved in 0.5 mL of DMF to form solution II. The zinc nitrate solution is added to the solution I, and after stirring for 5-10 min, the solution II is continuously added and stirred for 3-5 min to obtain a CZ solution. S2. Coating MnO2 1 mL of KMnO4 aqueous solution with a concentration of 50 mg / mL is added dropwise to the above-mentioned CZ solution under stirring at 500-700 rpm, and the stirring is continued at room temperature for 30 min to obtain a brown-yellow solution. After the reaction is completed, the solution is centrifuged at a speed of 12000 rpm for 10 min, the supernatant is dialyzed in a dialysis bag for 48 h, and then the precipitate is freeze-dried and stored at-20 o C.

[0026] The CA@ZIF-8 / MnO2 (referred to as CZM) prepared by the method has a dual function of self-consumption of GSH and self-supply of H2O2, and realizes the dual enhancement of CDT. 2+ When the CZM nanoparticles are internalized by tumor cells, the outer MnO2 is catalytically reacted with endogenous H2O2 to realize tumor-specific conversion, and Mn

[0027] The self-supplying hydrogen peroxide composite nanoparticles prepared by the method are applied to the preparation of an antitumor drug.

[0028] The method has the following technical effects: The CA@ZIF-8 nanoparticles are prepared by the in-situ loading method, and the problems of poor water solubility and easy degradation of CA can be solved, and the CZM nanoparticles with a uniform MnO2 shell layer are prepared by adjusting the reaction of CA and ZIF-8 with KMnO4, the self-oxidation characteristics of CA are effectively utilized, the CDT reaction is provided with continuous H2O2 reactant supply, the excessive antioxidant substance GSH in tumor cells is consumed, the purpose of improving the CDT treatment of cancer is achieved, the sequence of consuming GSH and then generating free radicals is effectively formed, and the synergistic antitumor effect of MnO2 and CA is effectively improved. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 The electron microscope images of the ZIF-8 and CA@ZIF-8 nanoparticles prepared in Example 1 of the application ((a) is ZIF-8, and (b) is CA@ZIF-8).

[0030] Figure 2 The electron microscope images of the CA@ZIF-8 nanoparticles prepared in Comparative Example 1 and Comparative Example 2 ((a) is Comparative Example 1, and (b) is Comparative Example 2).

[0031] Figure 3 The MB absorption spectrum changes caused by the CZM nanoparticles prepared in Example 1 of the application and different concentrations of H2O2.

[0032] Figure 4 The degradation effects of the Mn 2+ mediated Fenton-like reaction on MB under different GSH concentrations.

[0033] Figure 5 Degradation effect of MB by Fenton-like reaction induced by CZM nanoparticles prepared in Example 1 of the present application at different GSH concentrations.

[0034] Figure 6 In vitro cytotoxicity of different samples on 4T1 cells.

[0035] Figure 7 Results of particle size change of CZM nanoparticles prepared in the present application in aqueous solution and PBS after 7 days of placement. DETAILED DESCRIPTION

[0036] The present application will be described in detail below by way of examples. It is necessary to point out here that the following examples are only used to further illustrate the present application and cannot be understood as limiting the scope of protection of the present application. Those skilled in the art can make some non-essential improvements and adjustments to the present application according to the above content of the present application.

[0037] Preparation of ZIF-8 nanoparticles without loading, the specific steps are as follows: 75 mg of zinc nitrate hexahydrate was dissolved in 2.5 mL of deionized water to obtain a zinc nitrate solution, 165 mg of 2-methylimidazole was dissolved in 4.5 mL of methanol to obtain an imidazole solution, the zinc nitrate solution was quickly added to the imidazole solution under the condition of stirring at room temperature, until the solution appeared milky white, indicating that ZIF-8 nanoparticles had begun to form, and the stirring was continued for 3 min to ensure complete crystallization. The solution was separated by solid-liquid separation at 14000 rpm for 10 min, the precipitate was washed with deionized water for 3 times to remove the unreacted reagents, and the product was freeze-dried to obtain ZIF-8 nanoparticles.

[0038] Example 1 A self-supplying hydrogen peroxide composite nanoparticle, comprising the following steps: S1. Preparation of CA@ZIF-8 nanoparticles 75 mg of zinc nitrate hexahydrate was dissolved in 2.5 mL of deionized water to form a zinc nitrate solution, 165 mg of 2-methylimidazole was dissolved in 4.5 mL of methanol to obtain solution I, 10 mg of CA was dissolved in 0.5 mL of DMF to obtain solution II, the zinc nitrate solution was added to solution I, after stirring for 8 min, solution II was continuously added and stirred until the solution appeared milky white, and the stirring was continued for 4 min to obtain a CZ solution; S2. Coating MnO2 A 1 mL aqueous solution of KMnO4 with a concentration of 50 mg / mL was added dropwise to the above CZ solution under stirring at 600 rpm, and the solution was continuously stirred at room temperature for 30 min. After the reaction was completed, the solution was centrifuged at a speed of 12000 rpm for 10 min, and the supernatant was dialyzed in a dialysis bag for 48 h. Then, the precipitate was freeze-dried at -20 o C and stored.

[0039] The microstructures of the ZIF-8 nanoparticles without any load and the CA@ZIF-8 nanoparticles prepared in this example are shown in Figs. 1 and 2, respectively. Figure 1 It can be seen that the CA@ZIF-8 nanoparticles prepared in this example have a uniform morphology and excellent dispersibility, and the original morphology of ZIF-8 is well maintained.

[0040] Comparative Example 1 Different from Example 1, after the complete reaction of the zinc nitrate solution and solution I to form ZIF-8, solution II was added to load CA, and the remaining steps were the same as those in Example 1.

[0041] Since a large amount of CA is loaded on the surface of ZIF-8, the multi-groups in the high-concentration CA combine with the metal ions on the surface of ZIF-8 to form a bridging structure, resulting in the mutual attraction of adjacent nanoparticles to form agglomeration, as shown in Fig. 3 (a). Figure 2 During the wrapping of MnO2, a large amount of CA undergoes a redox reaction (the phenolic hydroxyl group of CA has reducing property) with the MnO2 precursor KMnO4, causing the MnO2 to be partially reduced to Mn 2+ , which reduces its catalytic activity of GSH. After the CA is loaded by the above post-loading method, the subsequent MnO2 grows excessively in the aggregation area, and the uniformity of the shell layer decreases, which adversely affects the release of the subsequent CA.

[0042] Comparative Example 2 Different from Example 1, in the preparation of the CA@ZIF-8 nanoparticles, solution I, the zinc nitrate solution and solution II were mixed and reacted together, and the remaining steps were the same as those in Example 1.

[0043] In this test process, the premature contact of CA with the ZIF-8 precursor solution leads to severe degradation of CA and competitive coordination, which hinders the growth of the target crystal. At the same time, the self-aggregation of CA leads to the aggregation of the final nanoparticles, as shown in Fig. 4 (b). Figure 2 The CA is wrapped in the interior of ZIF-8 in a large amount, and the regulation of the subsequent wrapped MnO2 shell layer decreases, and the uniformity of the wrapped shell layer decreases.

[0044] ZIF-8 and CA@ZIF-8 nanoparticles prepared in Example 1 were not loaded with CA as shown in Figure 1 CA@ZIF-8 in Comparative Example 1 and Comparative Example 2 were loaded with CA as shown in Figure 2 The particle size and morphology of the product of Example 1 were uniform, and the product was dispersed in the form of spherical particles, while the products prepared in Comparative Example 1 and Comparative Example 2 showed obvious agglomeration, which significantly reduced the loading efficiency of CA and also had an adverse effect on the subsequent loading and coating of MnO2.

[0045] The loading efficiency of CA directly affects the anti-tumor effect of nanoparticles and the persistence of solving the problem of endogenous H2O2 deficiency. High loading of CA can significantly improve the production of H2O2 in the tumor microenvironment and prolong the release time. The CZM synthesized by Example 1, Comparative Example 1 and Comparative Example 2 was tested by ultraviolet-visible spectrophotometry to test the chlorogenic acid absorbance, combined with the standard curve to calculate the concentration, and then the loading efficiency of CA was calculated. The calculated CA loading in the CZM prepared in Example 1, Comparative Example 1 and Comparative Example 2 was 11.8%, 4.9% and 9.6% respectively. Since CA in Comparative Example 1 is loaded on the surface of ZIF-8 by diffusion into the pores or surface adsorption, it is limited by the pore size, specific surface area of ZIF-8 and the affinity of chlorogenic acid and the carrier, resulting in low CA loading. Although the loading efficiency in Comparative Example 2 is significantly higher than that in Comparative Example 1, the raw material degradation is serious, resulting in lower loading than Example 1, and since CA is mainly wrapped inside ZIF-8, the uniformity of the subsequent MnO2 coating is poor, which has an adverse effect on the subsequent synergistic effect of CA and MnO2.

[0046] Chemical kinetics test: Mn 2+ Catalytic H2O2 can generate •OH to induce tumor cell apoptosis. To explore the generation activity of •OH and the scavenging effect of glutathione (GSH) on •OH, we selected methylene blue (MB) which can be degraded by •OH as an indicator. As shown in Figure 3 After adding CZM nanoparticles, MB was degraded, and with the increase of H2O2 concentration, the absorbance of MB showed a decreasing trend, and the color of the solution gradually changed from blue to transparent, indicating that the generation of •OH gradually increased, indicating that the intensity of the Fenton-like reaction depended on the concentration of H2O2.

[0047] It is worth noting that the active oxygen scavenger GSH can neutralize •OH, thereby weakening the active oxygen-based treatment effect. Overexpression of GSH in tumor cells directly hinders the efficiency of CDT, while reducing the intracellular GSH level can enhance the effectiveness of active oxygen therapy. Unlike Mn 2+ , MnO2 can preferentially consume GSH to generate Mn2+ Thus, it exhibits stronger •OH generation potential. Figure 4 It is confirmed that increasing GSH concentration will weaken the efficiency of Mn 2+ mediated Fenton-like reaction. In contrast, in CZM NPs mediated Fenton-like catalytic reaction, the inhibitory effect of GSH is significantly weakened, and the degradation of MB is enhanced under different GSH concentrations ( Figure 5 ). This phenomenon is due to the fact that in physiological environment, GSH reacts with MnO2 on the surface of CZM NPs to generate Mn 2+ , which makes CZM NPs with enhanced GSH depletion ability to effectively offset the impact of GSH in advance, and then generate •OH through CA to effectively promote the degradation of MB.

[0048] The results confirm that CZM NPs have good active oxygen species generation ability, and can consume excess antioxidant GSH in tumor cells, while the loaded CA has the characteristics of self-oxidation, which can provide continuous H2O2 reactant supply for CDT reaction, producing CDT self-enhancing effect.

[0049] Nanoparticle cancer cell killing test: The obtained nanoparticles were incubated with different cells, and laser confocal microscopy was used to evaluate their cell uptake ability, and MTT, flow cytometry and the like were used to evaluate their killing ability on 4T1 tumor cells. As shown in Figure 6 , CA and ZM NPs (MnO2 coated by ZIF-8) respectively exhibit concentration-dependent cytotoxicity through single chemotherapy or chemical dynamic therapy (CDT). It is worth noting that under the same CA concentration, CZM NPs exhibit better cytotoxicity than single functional nanoparticles due to the synergistic catalytic cascade reaction. In addition, the MTT determination of CZM NPs on HeLa cells and HepG2 cells also showed similar results, which demonstrated that CZM NPs have broad-spectrum in vitro anticancer potential.

[0050] Nanoparticle stability: CZM nanoparticles loaded with CA and coated with MnO2 shell were prepared, which could keep the particle size basically unchanged in aqueous solution at room temperature and 37 o C simulated physiological conditions (PBS buffer containing 10% FBS) for 7 days, as shown in Figure 7 , which shows that the nanomaterial has good size stability, and significantly improves the CDT efficacy by self-supplying hydrogen peroxide and synergistically enhancing Fenton-like reaction, which is of great significance for the storage and practical application of nanoparticles.

[0051] Example 2 A self-supplying hydrogen peroxide composite nanoparticle, comprising the following steps: S1. Preparation of CA@ZIF-8 nanoparticles Dissolve 70 mg of zinc nitrate hexahydrate in 2.5 mL of deionized water to form a zinc nitrate solution, dissolve 157.5 mg of 2-methylimidazole in 4.5 mL of methanol to form solution I, dissolve 9 mg of CA in 0.5 mL of DMF to form solution II, add the zinc nitrate solution to solution I, continue to stir for 5 min, then continue to add solution II and stir until the solution appears milky white, continue to stir for 5 min, and obtain a CZ solution; S2. Coating MnO2 Add 1 mL of KMnO4 aqueous solution with a concentration of 50 mg / mL dropwise to the above-mentioned CZ solution under stirring at 500 rpm, continue to stir at room temperature for 30 min, finally obtain a yellowish brown solution, after the reaction is completed, centrifuge the solution at a speed of 12000 rpm for 10 min, dialyze the supernatant with a dialysis bag for 48 h, then freeze-dry the precipitate, and store it at -20 o C.

[0052] Example 3 A self-supplying hydrogen peroxide composite nanoparticle comprises the following steps: S1. Preparation of CA@ZIF-8 nanoparticles Dissolve 80 mg of zinc nitrate hexahydrate in 2.5 mL of deionized water to form a zinc nitrate solution, dissolve 171 mg of 2-methylimidazole in 5 mL of methanol to form solution I, dissolve 11 mg of CA in 0.5 mL of DMF to form solution II, add the zinc nitrate solution to solution I, continue to stir for 10 min, then continue to add solution II and stir until the solution appears milky white, continue to stir for 5 min, and obtain a CZ solution; S2. Coating MnO2 Add 1 mL of KMnO4 aqueous solution with a concentration of 50 mg / mL dropwise to the above-mentioned CZ solution under stirring at 700 rpm, continue to stir at room temperature for 30 min, finally obtain a yellowish brown solution, after the reaction is completed, centrifuge the solution at a speed of 12000 rpm for 10 min, dialyze the supernatant with a dialysis bag for 48 h, then freeze-dry the precipitate, and store it at -20 o C.

Claims

1. A self-supplying hydrogen peroxide composite nanoparticle, characterized in that: The composite nanoparticles are based on ZIF-8 as a carrier, in situ loaded with chlorogenic acid CA to form CA@ZIF-8 nanoparticles, and coated with a layer of MnO2 shell layer of CA@ZIF-8 / MnO2 nanoparticles, which are recorded as CZM nanoparticles.

2. The self-supplying hydrogen peroxide composite nanoparticle according to claim 1, characterized in that: The CA@ZIF-8 nanoparticles are prepared by dissolving zinc nitrate hexahydrate in deionized water to form a zinc nitrate solution, dissolving 2-methylimidazole in methanol to form a solution I, and dissolving chlorogenic acid CA in DMF to obtain a solution II. The zinc nitrate solution is added to the solution I, stirred for 5 to 10 minutes, and then the solution II is added and stirred until the solution becomes milky white, and the stirring is continued for 3 to 5 minutes.

3. A method for preparing self-sufficient hydrogen peroxide composite nanoparticles, characterized in that: The method includes the steps of preparing CA@ZIF-8 nanoparticles and coating with MnO2. The preparation of CA@ZIF-8 nanoparticles is carried out by dissolving zinc nitrate hexahydrate in deionized water to form a zinc nitrate solution, dissolving 2-methylimidazole in methanol to form a solution I, dissolving chlorogenic acid CA in DMF to obtain a solution II, adding the zinc nitrate solution to the solution I, stirring for 5 to 10 minutes, and then continuously adding the solution II and stirring until the solution becomes milky white. The stirring is continued for 3 to 5 minutes to obtain a CA@ZIF-8 nanoparticle solution, which is recorded as CZ solution.

4. The method for preparing self-sufficient hydrogen peroxide composite nanoparticles according to claim 3, wherein: In the zinc nitrate solution, the mass volume ratio of zinc nitrate hexahydrate to deionized water is 28-32 mg:1 mL.

5. The method for preparing self-sufficient hydrogen peroxide composite nanoparticles according to claim 3 or 4, characterized in that: In the solution I, the mass volume ratio of 2-methylimidazole to methanol is 35-38 mg:1 mL.

6. The method for preparing self-sufficient hydrogen peroxide composite nanoparticles according to claim 5, wherein: The mass volume ratio of CA to DMF in the solution II is 18-22 mg:1 mL.

7. The method for preparing self-sufficient hydrogen peroxide composite nanoparticles according to claim 6, wherein: The volume ratio of the zinc nitrate solution, solution I and solution II is 0.45-0.55:0.8-1.2:0.

1.

8. The method for preparing self-sufficient hydrogen peroxide composite nanoparticles according to claim 7, wherein: The coated MnO2 is prepared by adding a KMnO4 aqueous solution dropwise to the above-mentioned CZ solution under stirring, and continuously stirring at a rate of 500-700 rpm for 25-35 minutes at room temperature to obtain a brown-yellow solution. After the reaction is completed, the solution is centrifuged at a speed of 10,000-13,000 rpm for 8-12 minutes, the centrifugal supernatant is dialyzed for 48 hours, and then the precipitate is freeze-dried.

9. The method for preparing self-sufficient hydrogen peroxide composite nanoparticles according to claim 8, wherein: The concentration of the KMnO4 aqueous solution is 48-52 mg / L, and the volume ratio of the KMnO4 aqueous solution to the CZ solution is 1:7-9.

10. Use of the self-supplied hydrogen peroxide composite nanoparticles prepared by the method according to claim 9 in the preparation of anti-tumor drugs.

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