Core-shell nanocomposites prepared by in-situ growth based on sacrificial template and its application in promoting healing of infected wounds

Abstract

This invention discloses a core-shell nanocomposite material prepared by sacrificial template in situ growth and its application in promoting the healing of infected wounds. The present invention is the first to use ZnO2@ZIF-8 as an acid-responsive H2O2 release source to construct a ZnO2@Hemin-ZIF-8@PB composite nanomaterial. This material remains stable in a neutral environment, triggers H2O2 release in the infected microenvironment, and achieves efficient antibacterial and biofilm clearance through the synergistic effect of Hemin / PB-mediated chemical kinetics and Prussian blue (PB) photothermal effect. At the same time, this material can regulate the inflammatory response and promote angiogenesis, thereby accelerating the repair of infected wounds.

Description

Technical Field

[0001] This invention relates to the fields of nanobiomaterials and pharmaceutical technology, and in particular to core-shell nanocomposites prepared by sacrificial template in situ growth and their application in promoting the healing of infected wounds. Background Technology

[0002] Bacterial infection, especially drug-resistant bacteria and biofilm formation, is a major barrier to the prolonged healing of chronic wounds in clinical settings (such as diabetic foot ulcers and burn wounds). The highly complex extracellular polymeric substance (EPS) matrix within biofilms constitutes a robust physical diffusion barrier, not only limiting the deep penetration of traditional antibiotics but also inducing bacteria into a metabolic dormant state, resulting in extremely high biofilm resistance and severely hindering the wound healing process. In recent years, chemokinetic therapy (CDT) based on metal peroxides (such as ZnO2) as endogenous H2O2 donors has shown great potential in the field of antibacterial treatment. However, ZnO2 is highly susceptible to spontaneous pre-hydrolysis in a physiologically neutral environment (pH 7.4), which not only leads to poor chemical stability of the material and the inability to control reactive oxygen species (ROS) generation as needed but also results in potential systemic toxicity due to premature release of H2O2. Existing preparation strategies, such as the one-pot co-precipitation method, have high requirements for the dispersibility and particle size of peroxides, and often result in incomplete or uneven coating or distribution of the peroxide core, making it difficult to achieve complete and effective shielding of the active component on a spatiotemporal scale. Therefore, there is an urgent need to develop a highly efficient nanoplatform that is independent of the morphology, size, and dispersibility of peroxides, maintains high stability during cycling, and can precisely trigger cascade catalytic reactions in the acidic microenvironment of the infection site. This has profound clinical significance for achieving precise repair of infected wounds. Summary of the Invention In view of this, the purpose of this invention is to propose a core-shell nanocomposite material prepared by sacrificial template in situ growth and its application in promoting the healing of infected wounds. This scheme proposes a ZnO2@ZIF-8 core-shell nanoparticle with high structural density and pH-responsive H2O2 release characteristics, and its preparation method. Through the sacrificial template in situ growth strategy, a dense ZIF-8 shell is constructed on the ZnO2 surface, thereby inhibiting the hydrolysis of ZnO2 in aqueous solution and achieving acid-responsive H2O2 release. Based on the aforementioned material structure, this scheme also proposes to introduce heme (Hemin) and Prussian blue (PB) to construct ZnO2@Hemin-ZIF-8@PB composite nanomaterials (i.e., core-shell nanocomposite materials) and their preparation method. This material is activated in the weakly acidic microenvironment of infected wounds, achieving highly efficient antibacterial activity and promoting tissue repair through the synergistic effect of nanozyme cascade catalysis and photothermal effect.

[0003] To achieve the above-mentioned technical objectives, the technical solution adopted by this invention is as follows: A core-shell nanocomposite material (ZnO2@Hemin-ZIF-8@PB) prepared by sacrificial template in situ growth method is described. It uses zinc peroxide (ZnO2) nanoparticles as the active core and metal-organic framework ZIF-8 as a dense protective shell layer grown in situ on the surface of the zinc peroxide nanoparticles. The metal-organic framework ZIF-8 is loaded with hemin inside and hyaluronic acid (HA) and Prussian blue (PB) on its surface.

[0004] The metal-organic framework ZIF-8 is a dense coating structure with atomic-level interface bonding formed by using the zinc peroxide nanoparticles as the sole zinc source and as a sacrificial template through a sacrificial template-guided in-situ growth method. It is used to inhibit the pre-hydrolysis of the zinc peroxide nanoparticles under physiologically neutral conditions.

[0005] As one possible implementation, the heme described in this scheme is loaded into the framework or cavity of the metal-organic framework ZIF-8 through in-situ self-assembly; the Prussian blue is anchored on the surface of the metal-organic framework ZIF-8 through the mediation of hyaluronic acid; the hyaluronic acid also serves as a targeting ligand and a wound repair promoting factor.

[0006] As a possible implementation, the core-shell nanocomposite material described in this scheme further exhibits microenvironment-responsive characteristics. It maintains structural stability under neutral physiological conditions, and under acidic microenvironment conditions such as an infected wound with a pH of 5.0 to 6.5 or other acidic conditions, the metal-organic framework ZIF-8 undergoes responsive dissociation to trigger the hydrolysis of the zinc peroxide nanoparticles, which serve as the active core, thereby releasing hydrogen peroxide.

[0007] Based on the above, this scheme also proposes a method for preparing the core-shell nanocomposite material prepared by the sacrificial template in-situ growth method. This method uses ZnO2@ZIF-8 as the acid-responsive H2O2 release source and employs a stepwise synthesis strategy. First, a ZnO2@Hemin-ZIF-8 intermediate is prepared, and then Prussian blue (PB) is loaded onto it to obtain the ZnO2@Hemin-ZIF-8@PB composite nanomaterial. The specific steps include: (1) Zinc peroxide (ZnO2) nanoparticles were prepared by precipitation method. The zinc peroxide nanoparticles were dispersed in an organic solvent containing 2-methylimidazole to form a reaction system. If a shell loaded with heme (Hemin) is to be prepared, Hemin is added to the reaction system. (2) The reaction system is placed under solvothermal conditions, using zinc ions slowly released from the surface of zinc peroxide as the sole metal source (Zn). 2+The reaction system guides the in-situ growth of ZIF-8 on its surface to obtain an intermediate (ZnO2@ZIF-8 core-shell structure); if Hemin is added to the reaction system, an intermediate loaded with heme (ZnO2@Hemin-ZIF-8 core-shell structure) can be prepared. (3) The intermediate is mixed with hyaluronic acid solution for surface functionalization, and finally mixed with Prussian blue solution. The core-shell nanocomposite material is obtained by electrostatic assembly or chemical chelation. That is, Prussian blue is loaded on the surface of ZnO2@ZIF-8 or ZnO2@Hemin-ZIF-8 through hyaluronic acid to obtain ZnO2@ZIF-8@PB or ZnO2@Hemin-ZIF-8@PB composite nanomaterials.

[0008] As a possible implementation, further, in steps (1) and (2) of this scheme, the ZnO2@ZIF-8 nanoparticles, which serve as the acid-response release source of H2O2, are prepared by a solvothermal method. 2-Methylimidazole is dissolved in an organic solvent, followed by the addition of an organic solvent dispersion of ZnO2. After thorough mixing, the mixture is transferred to a stainless steel reactor lined with polytetrafluoroethylene (PTFE) for reaction. After the reaction is complete, the mixture is naturally cooled to room temperature, the product is collected by centrifugation, washed with methanol, and then dried to obtain ZnO2@ZIF-8 nanoparticles.

[0009] The organic solvent is one or more common mixed solutions such as methanol, ethanol, propanol, butanol, DMF, DMSO, DMA, DEF, dimethylpyrrolidone, and acetone; the concentration of the 2-methylimidazole is 0.01–500 M; and the concentration of ZnO2 in the organic solvent dispersion is 0.01–500 mg / mL. -1 The solvothermal reaction temperature is 30–300 °C; the reaction time is 0.1–120 h; the drying temperature is 20–200 °C, and the drying time is 0.1–120 h.

[0010] As a possible implementation method, further, in step (2) of this scheme, the reaction temperature under the solvothermal conditions is 30-180 ℃ and the reaction time is 0.1-120 hours; by controlling the reaction parameters, the thickness of the ZIF-8 generated by the reaction is between 5-600 nm, so as to adjust its protective effect on the zinc peroxide central core.

[0011] As another possible implementation, further, if the shell loaded with hemin is to be prepared, hemin is added to the reaction system. Accordingly, in steps (1) and (2), 2-methylimidazole is dissolved in an organic solvent, ZnO2 nanoparticles dispersed in the organic solvent are added, and hemin dissolved in the organic solvent is added. After mixing evenly, the mixture is transferred to a hydrothermal reactor and reacted at a set temperature. After the reaction is completed, the mixture is naturally cooled, the product is collected by centrifugation, washed with methanol, and dried to obtain the material ZnO2@Hemin-ZIF-8.

[0012] The concentration of the 2-methylimidazole is 0.01–500 M; the concentration of the ZnO2 dispersion is 0.01–500 mg / mL. -1 The concentration of Hemin is 0.0001–100 M; the Hemin is dissolved in an organic solvent such as DMSO, methanol or ethanol; the reaction is carried out in a hydrothermal reactor under solvothermal conditions, with a set temperature of 20–300 °C; the drying temperature is set at 20–200 °C, and the drying time is 0.1–120 h.

[0013] For step (3), as a possible implementation, step (3) of this scheme further includes: mixing the ZnO2@Hemin-ZIF-8 intermediate obtained in step (2) with hyaluronic acid at a certain mass ratio, stirring the reaction at room temperature to form a coating layer on the surface of hyaluronic acid; after the reaction is completed, collecting the product by centrifugation and washing it with deionized water to obtain the HA-modified ZnO2@Hemin-ZIF-8+HA intermediate.

[0014] Subsequently, the above product (the intermediate of HA-modified ZnO2@Hemin-ZIF-8+HA) was redispersed in deionized water, and Prussian blue nanoparticle dispersion was added. The reaction was continued by stirring to achieve electrostatic self-assembly. After the reaction was completed, the product was collected by centrifugation and washed with deionized water to obtain ZnO2@Hemin-ZIF-8@PB composite nanomaterials.

[0015] The mass ratio of ZnO2@Hemin-ZIF-8 to hyaluronic acid is 1:0.01–1:200; the hyaluronic acid coating reaction time is 0.1–300 h; and the concentration of the ZnO2@Hemin-ZIF-8 intermediate dispersed in deionized water is 0.01–500 mg / mL. -1 The concentration of the Prussian blue nanoparticle dispersion is 0.01–500 mg / mL. -1 The electrostatic self-assembly reaction time is 0.1–300 h.

[0016] Based on the above, this solution also proposes the application of the core-shell nanocomposite material prepared by the sacrificial template in situ growth method in the preparation of drugs or medical dressings that promote the healing of infected wounds.

[0017] The core-shell nanocomposite material prepared by the sacrificial template in situ growth method involved in this scheme maintains structural stability under neutral conditions such as pH 7.4, and triggers the release of H2O2 from ZnO2 under slightly acidic conditions such as pH 5.0–6.5 in the acidic microenvironment of infected wounds. Through the synergistic effect of acid-responsive activated chemokinetic therapy and near-infrared light-driven photothermal therapy, effective clearance of bacteria and biofilms is achieved. At the same time, by downregulating the expression of pro-inflammatory factors TNF-α and IL-6 and upregulating the expression of CD31, the inflammatory response is reduced and angiogenesis is promoted, thereby accelerating tissue repair.

[0018] As one possible implementation, the method for promoting the healing of infected wounds further includes synergistic sterilization and tissue regeneration regulation; wherein, sterilization is achieved through the synergistic effect of dual chemokinetic therapy (CDT) triggered by the infectious microenvironment and near-infrared photothermal therapy (PTT).

[0019] As one possible implementation, the application described in this scheme further includes modulating the wound immune microenvironment by downregulating the expression of pro-inflammatory factors at the wound site, and promoting angiogenesis by upregulating the expression of CD31.

[0020] As one possible implementation, further, the infectious wound described in this scheme is a chronic, difficult-to-heal wound containing a bacterial biofilm, and the core-shell nanocomposite material is used to penetrate the biofilm matrix and clear pathogens.

[0021] By adopting the above technical solution, the present invention has the following beneficial effects compared with the prior art: The present invention is the first to use ZnO2@ZIF-8 as the acid-responsive release source of H2O2 to construct a ZnO2@Hemin-ZIF-8@PB composite nanomaterial. This material remains stable in a neutral environment, triggers the release of H2O2 in the infected microenvironment, and achieves efficient antibacterial and biofilm clearance through the synergistic effect of Hemin / PB-mediated chemical kinetics and Prussian blue (PB) photothermal effect. At the same time, this material can regulate the inflammatory response and promote angiogenesis, thereby accelerating the repair of infected wounds. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 TEM image of ZnO2@ZIF-8 nanoparticles prepared in an embodiment of the present invention; Figure 2 TEM image of ZnO2@Hemin-ZIF-8 nanoparticles prepared in an embodiment of the present invention; Figure 3 TEM image of ZnO2@Hemin-ZIF-8@PB nanoparticles prepared in an embodiment of the present invention; Figure 4 The killing effect of ZnO2@Hemin-ZIF-8@PB nanoparticles prepared in this embodiment of the invention on Staphylococcus aureus before and after irradiation with 808nm laser light; Figure 5 The killing effect of ZnO2@Hemin-ZIF-8@PB nanoparticles prepared in this embodiment of the invention on Escherichia coli before and after irradiation with 808nm laser light; Figure 6 The killing effect of ZnO2@Hemin-ZIF-8@PB nanoparticles prepared in this embodiment of the invention on the mature biofilm of Staphylococcus aureus before and after irradiation with 808nm laser light; Figure 7 The effect of ZnO2@Hemin-ZIF-8@PB nanoparticles prepared in this embodiment of the invention on the inhibition of Staphylococcus aureus biofilm growth before and after irradiation with 808nm laser light; Figure 8 The effect of ZnO2@Hemin-ZIF-8@PB nanoparticles prepared in this invention on the repair of Staphylococcus aureus-infected mouse wounds after irradiation with 808nm laser light; Figure 9 The image shows a comparison of the characterization of the ZnO2@Hemin-ZIF-8@PB nanoparticles prepared in this invention, using immunohistochemistry to detect the expression levels of inflammation and angiogenesis-related factors. Detailed Implementation

[0024] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be particularly noted that the following embodiments are for illustrative purposes only and do not limit the scope of the invention. Similarly, the following embodiments are only some, not all, embodiments of the present invention, and all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] This embodiment proposes a core-shell nanocomposite material prepared by sacrificial template in situ growth method. It uses zinc peroxide nanoparticles as active core and metal-organic framework ZIF-8 as dense protective shell layer grown in situ on the surface of zinc peroxide nanoparticles. The metal-organic framework ZIF-8 is loaded with heme inside and hyaluronic acid and Prussian blue are loaded on its surface. The metal-organic framework ZIF-8 is a dense coating structure with atomic-level interface bonding formed by using the zinc peroxide nanoparticles as the sole zinc source and as a sacrificial template through a sacrificial template-guided in-situ growth method. It is used to inhibit the pre-hydrolysis of the zinc peroxide nanoparticles under physiologically neutral conditions.

[0026] In this scheme, the heme is loaded into the framework or cavity of the metal-organic framework ZIF-8 through in-situ self-assembly; the Prussian blue is anchored on the surface of the metal-organic framework ZIF-8 through the mediation of hyaluronic acid; the hyaluronic acid also serves as a targeting ligand and a wound repair promoting factor.

[0027] In this scheme, the core-shell nanocomposite material has microenvironment responsive characteristics. It maintains structural stability under neutral physiological conditions, and under acidic microenvironment conditions such as infected wounds with pH 5.0~6.5 or other acidic conditions, the metal-organic framework ZIF-8 will undergo responsive dissociation to trigger the hydrolysis of zinc peroxide nanoparticles, which serve as the active core, thereby releasing hydrogen peroxide.

[0028] The following section further elaborates on the preparation method and application verification of the core-shell nanocomposite material prepared by the sacrificial template in-situ growth method: (1) Preparation of ZnO2@ZIF-8: 2.62 g of 2-methylimidazole was dissolved in 4.0 mL of methanol, followed by the addition of 2.75 mL of a methanol dispersion of ZnO2. The resulting mixture was transferred to a stainless steel reactor lined with polytetrafluoroethylene (PTFE) and reacted at 80 °C for 48 h. After the reaction was completed, the mixture was allowed to cool naturally to room temperature. The product was collected by centrifugation, washed three times with methanol, and finally dried under vacuum at 60 °C overnight to obtain ZnO2@ZIF-8 nanoparticles.

[0029] See Figure 1As can be seen from the TEM results, the ZnO2@ZIF-8 prepared in this case has reached the nanoscale size.

[0030] (2) Preparation of ZnO2@Hemin-ZIF-8: To synthesize ZnO2@Hemin-ZIF-8 nanoparticles, a similar synthesis procedure as described above was employed, except that 1.0 mg of Hemin (pre-dissolved in 1 mL DMSO) was introduced into the methanol dispersion of ZnO2 before adding 2-methylimidazole. All other reaction conditions and subsequent purification steps remained consistent with the preparation process of ZnO2@ZIF-8 nanoparticles.

[0031] See Figure 2 As can be seen from the TEM results, the ZnO2@Hemin-ZIF-8 prepared in this case has reached the nanoscale size.

[0032] (3) Preparation of ZnO2@Hemin-ZIF-8@PB: To prepare ZnO2@Hemin-ZIF-8@PB nanocomposites, ZnO2@Hemin-ZIF-8 was mixed with hyaluronic acid (HA) at a mass ratio of 1:10 and stirred for 12 h to promote HA coating on its surface. Subsequently, the HA-modified ZnO2@Hemin-ZIF-8 was collected by centrifugation and thoroughly washed with deionized water. Next, the resulting solid product was redispersed in 10 mL of deionized water and mixed with 4 mL of the Prussian blue nanoparticle (PB NPs) dispersion prepared above. After continuous stirring for 24 h to achieve electrostatic self-assembly, the final product ZnO2@Hemin-ZIF-8@PB was collected by centrifugation and thoroughly washed with deionized water. See [link to product details] Figure 3 As can be seen from the TEM results, the ZnO2@Hemin-ZIF-8 prepared in this case has reached the nanoscale size.

[0033] (4) Application verification of ZnO2@Hemin-ZIF-8@PB as an antibacterial composite material The antibacterial properties were evaluated using the plate coating method, with Staphylococcus aureus (Staphylococcus aureus) as the target. S. aureus ) and Escherichia coli ( E. coli The strain in question was the model strain. The minimum bactericidal concentration (MBC) was determined by standard plate counting.

[0034] The specific method is as follows: Add 100 μL of bacterial suspension (1×10) 8 CFU·mL -1The sample was mixed with 100 μL of different sample dispersions and 800 μL of pH 5.0 acetate buffer; for the photothermal enhancement group, an 808 nm laser (1.0 W·cm⁻¹) was used after mixing. -2 Irradiate for 10 min. Then, incubate each system at 37 ℃ and 150 rpm for 12 h. After the reaction, take 30 μL of the reaction solution and spread it evenly on a solid agar plate, and incubate at 37 ℃ for 24 h. Quantitative evaluation of antibacterial activity is performed by counting colony forming units (CFUs). See [link to relevant documentation] Figure 4 , Figure 5 At a final concentration of 50 μg·mL -1 Under certain conditions, the ZnO2@Hemin-ZIF-8@PB composite nanomaterial exhibits good performance under both illuminated and unilluminated conditions. S. aureus and E. coli It exhibits good antibacterial properties.

[0035] (5) Validation of ZnO2@Hemin-ZIF-8@PB as an anti-biofilm The inhibition and scavenging ability of ZnO2@Hemin-ZIF-8@PB composite nanomaterials was demonstrated by Staphylococcus aureus (Staphylococcus aureus) S. aureus The model was evaluated.

[0036] To construct a mature biofilm, Staphylococcus aureus (1 × 10⁻⁶) was used. 8 CFU mL -1 The bacteria were inoculated into Mueller–Hinton broth (MHB) and incubated in 24-well plates at 37 °C for 48 h. After removing unadhered bacteria by gentle washing, 1 mL of ZnO2@Hemin-ZIF-8@PB or 50 μg / mL of ZnO2@Hemin-ZIF-8@PB was added. -1 Biofilms were treated. The corresponding treatment groups were further irradiated with an 808 nm near-infrared (NIR) laser (1.0 W cm⁻¹). -2 The biomass of the residual biofilm was quantified by crystal violet (CV) staining. Specifically, 200 μL of 1.0% (w / v) CV staining solution was added to each well and incubated for 30 min. See [link to relevant documentation] Figure 6 , Figure 7 Compared to the control group, ZnO2@Hemin-ZIF-8@PB exhibited superior anti-biofilm activity under laser irradiation.

[0037] (6) Application verification of ZnO2@Hemin-ZIF-8@PB composite nanomaterials for promoting the healing of infected wounds Male Balb / c mice (SPF grade, 6–8 weeks old, weighing 25 ± 2 g) were used to establish an infected wound model. After anesthesia and disinfection, a full-thickness skin defect with a diameter of 8 mm was prepared on the back of the mouse using a biopsy puncture instrument, and 100 μL of Staphylococcus aureus (S. aureus, 1 × 10⁻⁶) was inoculated into the wound. 8 CFU·mL - ¹), and then covered with sterile medical dressings for 24 h to establish an infection model. After infection was established, mice were randomly divided into a saline control group (Control) and a ZnO2@Hemin-ZIF-8@PB treatment group. Both groups were treated with 808 nm near-infrared laser (1.0 W·cm⁻¹). -2 Treatment was performed under 10-minute irradiation. The wound was photographed and the healing progress was assessed every two days. See [link / reference]. Figure 8 Compared with the control group, the wound in the ZnO2@Hemin-ZIF-8@PB treatment group was basically completely healed by day 8, while the wound in the control group healed slowly and showed no significant improvement.

[0038] (7) Application verification of ZnO2@Hemin-ZIF-8@PB composite nanomaterials for relieving inflammation at infected wound sites and promoting angiogenesis Based on the validation of the application of ZnO2@Hemin-ZIF-8@PB composite nanomaterials in promoting the healing of infected wounds, wound tissue was collected on day 8 for histological analysis. Immunohistochemistry was used to detect the expression levels of inflammation and angiogenesis-related factors, including IL-6, TNF-α, IL-10, and CD31. See also... Figure 9 Compared with the control group, the ZnO2@Hemin-ZIF-8@PB treatment group showed a significant reduction in inflammatory response, downregulation of pro-inflammatory factors IL-6 and TNF-α expression, and upregulation of anti-inflammatory factor IL-10 expression; at the same time, CD31 expression was significantly enhanced, indicating increased angiogenesis, thereby effectively promoting wound tissue repair.

[0039] The above description is only a part of the embodiments of the present invention and does not limit the scope of protection of the present invention. Any equivalent device or equivalent process transformation made based on the content of the present invention specification and drawings, or direct or indirect application in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A core-shell nanocomposite material prepared by in-situ growth using a sacrificial template, characterized in that, Using zinc peroxide nanoparticles as the active core, a metal-organic framework ZIF-8 is grown in situ on the surface of the zinc peroxide nanoparticles as a dense protective shell. The metal-organic framework ZIF-8 is loaded with heme inside and hyaluronic acid and Prussian blue are loaded on its surface. The metal-organic framework ZIF-8 is a dense coating structure with atomic-level interface bonding formed by using the zinc peroxide nanoparticles as the sole zinc source and as a sacrificial template through a sacrificial template-guided in-situ growth method. It is used to inhibit the pre-hydrolysis of the zinc peroxide nanoparticles under physiologically neutral conditions.

2. The core-shell nanocomposite material prepared by the sacrificial template in-situ growth method as described in claim 1, characterized in that, The heme is loaded into the framework or cavity of the metal-organic framework ZIF-8 through in-situ self-assembly; the Prussian blue is anchored on the surface of the metal-organic framework ZIF-8 through the mediation of hyaluronic acid; the hyaluronic acid also serves as a targeting ligand and a wound repair promoting factor.

3. The core-shell nanocomposite material prepared by the sacrificial template in-situ growth method as described in claim 1, characterized in that, The core-shell nanocomposite material has microenvironment responsive characteristics. It maintains structural stability under neutral physiological conditions, and under acidic microenvironment conditions such as infected wounds with pH 5.0~6.5 or other acidic conditions, the metal-organic framework ZIF-8 will undergo responsive dissociation to trigger the hydrolysis of zinc peroxide nanoparticles, which serve as the active core, thereby releasing hydrogen peroxide.

4. The method for preparing core-shell nanocomposite materials based on the in-situ growth method using a sacrificial template as described in any one of claims 1 to 3, characterized in that, It includes the following steps: (1) Disperse zinc peroxide nanoparticles in an organic solvent containing 2-methylimidazole to form a reaction system; (2) The reaction system is placed under solvothermal conditions and zinc ions slowly released from the surface of zinc peroxide are used as the only metal source to guide ZIF-8 to grow in situ on its surface to obtain an intermediate. (3) The intermediate is mixed with hyaluronic acid solution for surface functionalization, and finally mixed with Prussian blue solution to obtain the core-shell nanocomposite material by electrostatic assembly or chemical chelation.

5. The method for preparing core-shell nanocomposite materials based on in-situ growth using a sacrificial template as described in claim 4, characterized in that, In step (1), hemin is added to the reaction system; correspondingly, in step (2), ZIF-8 loaded with hemin is guided to grow in situ on the surface of zinc peroxide to obtain an intermediate.

6. The method for preparing the core-shell nanocomposite material based on the in-situ growth method using a sacrificial template as described in claim 4, characterized in that, In step (2), the reaction temperature under solvothermal conditions is 30-180 °C and the reaction time is 0.1-120 hours. By controlling the reaction parameters, the thickness of the ZIF-8 generated by the reaction is between 5-600 nm to adjust its protective efficacy against the zinc peroxide core.

7. The use of the core-shell nanocomposite material prepared by the sacrificial template in situ growth method as described in any one of claims 1 to 3, or the core-shell nanocomposite material prepared by the method described in any one of claims 4 to 6, in the preparation of drugs or medical dressings that promote the healing of infected wounds.

8. The application as described in claim 7, characterized in that, The promotion of infected wound healing includes synergistic sterilization and tissue regeneration regulation; wherein, sterilization is achieved through the synergistic effect of dual chemokinetic therapy CDT triggered by the infectious microenvironment and near-infrared driven photothermal therapy PTT.

9. The application as described in claim 7, characterized in that, The applications include modulating the wound immune microenvironment by downregulating the expression of pro-inflammatory factors at the wound site, and promoting angiogenesis by upregulating the expression of CD31.

10. The application as described in claim 7, characterized in that, The infectious wound is a chronic, difficult-to-heal wound containing a bacterial biofilm, and the core-shell nanocomposite material is used to penetrate the biofilm matrix and clear pathogens.

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