Nano-enzyme composite microneedle patch for treating acne and preparation method of nano-enzyme composite microneedle patch

Abstract

The invention discloses a nano-enzyme composite micro-needle patch for treating acne and a preparation method thereof, the nano-enzyme composite micro-needle patch comprises a micro-needle body and a micro-needle backing which are connected, the micro-needle body is made of gamma-polyglutamic acid, and sound-sensitive nanoparticles with enzyme-like performance are loaded on the micro-needle body. The nano-particles can penetrate through the epidermis to reach the acne lesion site and rapidly dissolve and release the nano-particles, the released nano-particles can convert inflammatory active oxygen in the acne inflammation microenvironment into oxygen, sonodynamic therapy is enhanced, and the hypoxic microenvironment of acne is improved. Meanwhile, the released nano-particles synergistically dissolved gamma-PGA can promote maturation of dendritic cells, ultrasonic mediated treatment and in-situ oxygen production are combined, antibacterial immune response is achieved, healing of acnes can be effectively promoted, secondary relapse can be prevented, and the nano-particles have good application prospects in clinical treatment of acnes.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a nano-enzyme composite microneedle patch for treating acne and a preparation method thereof. BACKGROUND

[0002] Acne is a common skin disease that affects more than 80% of the global population. If inflamed acne is not treated and managed in a timely manner, it often leads to pigmentation and permanent scarring, which has a profound negative impact on the quality of life and psychology of patients, including stress, anxiety, depression and psychological disorders.

[0003] Propionibacterium acnes is a lipophilic, gram-positive anaerobic bacterium, and its colonization of the pilosebaceous gland is considered to be the main cause of acne. The clogged hair follicles create a good local anaerobic environment, allowing Propionibacterium acnes to multiply rapidly, and the lipase produced by Propionibacterium acnes can decompose the triglycerides in sebum, further producing free fatty acids, which are the main factors leading to inflammatory lesions of acne. Therefore, killing and inhibiting Propionibacterium acnes is an effective measure for treating acne.

[0004] Currently, oral antibiotics or topical antibiotic creams are often used in clinical treatment of acne; however, due to the repeated occurrence of acne, frequent oral antibiotics can damage normal intestinal microorganisms and lead to the generation of bacterial drug resistance, in addition, the penetration of topical antibiotic creams into the skin is poor, and it is difficult to effectively kill bacteria. Therefore, it is necessary to develop a technical method that can effectively treat acne and prevent secondary recurrence of acne. SUMMARY

[0005] In view of the above problems, the present application aims to provide a nano-enzyme composite microneedle patch for treating acne and a preparation method thereof.

[0006] The technical solution of the present application is as follows: On the one hand, a nano-enzyme composite microneedle patch for treating acne is provided, which comprises a microneedle body and a microneedle backing connected together, the microneedle body is made of gamma-polyglutamic acid, and the microneedle body is loaded with sound-sensitive nanoparticles having enzyme-like properties.

[0007] As a preferred, the length of the needle tip of the nano-enzyme composite microneedle patch is 300-650 μm.

[0008] As a preferred, the microneedle backing is made of a biodegradable material.

[0009] As a preferred, the biodegradable material is any one or more of polyvinyl alcohol, gelatin, hyaluronic acid and polyvinylpyrrolidone.

[0010] As a preferred, the sonosensitizing nanoparticles with enzymatic-like properties are manganese porphyrin metal organic frameworks.

[0011] In another aspect, the application also provides a method for preparing the nano-enzyme composite microneedle patch for treating acne, comprising the following steps: S1: preparing sonosensitizing nanoparticles with enzymatic-like properties; S2: dissolving the microneedle backing material and gamma-polyglutamic acid in solvent I respectively, stirring until completely dissolved to obtain a microneedle backing pre-gel solution and a gamma-polyglutamic acid pre-gel solution; S3: uniformly dispersing the sonosensitizing nanoparticles with enzymatic-like properties in the gamma-polyglutamic acid pre-gel solution, and then adding the mixed solution into a microneedle mold to dry to obtain a microneedle mold filled with microneedle bodies; S4: adding the microneedle backing pre-gel solution into the microneedle mold filled with microneedle bodies, drying and demolding to obtain the nano-enzyme composite microneedle patch.

[0012] As a preferred, when the sonosensitizing nanoparticles with enzymatic-like properties are manganese porphyrin metal organic frameworks, step S1 specifically comprises the following sub-steps: dissolving tetracarboxylic tetraphenyl manganese porphyrin, benzoic acid and zirconyl chloride octahydrate in solvent II, and then stirring at 80-100℃ under light-proof conditions for 4-7h to obtain the sonosensitizing nanoparticles with enzymatic-like properties.

[0013] As a preferred, in step S2, the mass fraction of solute in the microneedle backing pre-gel solution is 10-40%, and the mass fraction of solute in the gamma-polyglutamic acid pre-gel solution is 10-60%.

[0014] As a preferred, in step S3, the concentration of the sonosensitizing nanoparticles with enzymatic-like properties in the gamma-polyglutamic acid pre-gel solution is 10-100μg / mL.

[0015] The application has the following beneficial effects: The application can penetrate the epidermis to reach the acne lesion site and quickly dissolve and release nanoparticles. The released nanoparticles can convert the inflammatory reactive oxygen species in the inflammatory microenvironment of acne into oxygen, enhance sonodynamic therapy and improve the hypoxic microenvironment of acne. At the same time, the released nanoparticles can promote the maturation of dendritic cells in cooperation with dissolved gamma-PGA, realize antibacterial immune response through ultrasound-mediated treatment and in-situ oxygen production, effectively promote the healing of acne and prevent secondary recurrence, and have a good application prospect in the clinical treatment of acne. BRIEF DESCRIPTION OF DRAWINGS

[0016] In order to make the technical solutions in the embodiments of the present application or the prior art clearer, the accompanying drawings needed in the embodiments or prior art description will be briefly introduced. Obviously, the accompanying drawings in the following description only show some embodiments of the present application, and other accompanying drawings can be obtained by those of ordinary skill in the art without any creative effort based on these accompanying drawings.

[0017] Figure 1 Figure 1 is a PCN222-Mn nanoparticle morphology chart in Example 1; wherein (A) is a scanning electron microscope chart of the nanoparticles; (B) is a transmission electron microscope chart of the nanoparticles; Figure 2 Figure 2 is a schematic diagram of PCN222-Mn nanoparticle catalysis of hydrogen peroxide to produce oxygen in different concentrations in Examples 1-3; Figure 3 Figure 3 is an electron spin resonance chart of PCN222-Mn nanoparticles producing singlet oxygen under different conditions in Example 1; Figure 4 Figure 4 is a morphology chart of the nanoscale enzyme composite microneedle patch in Example 1; wherein (A) is a fluorescence microscope chart of the composite microneedle patch; (B) is a scanning electron microscope chart of the composite microneedle patch; Figure 5 Figure 5 is a diagram of the effect of dissolving before and after the microneedle penetrating the pig skin in Example 1; wherein (A) is a morphology chart of the microneedle patch before penetrating the pig skin; (B) is a diagram of the ex vivo pig skin after the microneedle treatment; (C) is a morphology chart of the microneedle patch after penetrating the pig skin; Figure 6 Figure 6 is a diagram of the antibacterial efficiency of the nanoscale enzyme composite microneedle patch on P. acnes under different conditions in Example 1; Figure 7 Figure 7 is a schematic diagram of the promotion of DCs maturation by the antigens released by the death of bacteria treated by sonodynamic therapy, PCN222-Mn and the dissolution of the needle tip, and γ-PGA; wherein (A) is a flow cytometry analysis chart of DCs; (B) is a quantitative analysis chart of mature DCs; Figure 8 Figure 8 is a schematic diagram of the change in the thickness of acne in mice in different treatment groups; Figure 9 Figure 9 is a schematic diagram of the expression level of memory B cells after the nanoscale enzyme composite microneedle patch in Example 1 was used for sonodynamic therapy of acne; wherein (A) is a flow cytometry analysis chart of memory B cells after the mice were twice infected with P. acnes, (B) is a quantitative statistical chart, and (C) is an lgG antibody level expression chart; Figure 10 Figure 10 is a statistical chart of the thickness of acne in mice after the mice were twice infected with P. acnes in different treatment groups. DETAILED DESCRIPTION

[0018] The application will be further described below in conjunction with the drawings and examples. It should be noted that the examples in the present application and the technical features in the examples can be combined with each other without conflict. It should be noted that all the technical and scientific terms used in the present application have the same meaning as generally understood by those skilled in the art to which the present application belongs, unless otherwise specified. The "including" or "containing" and similar words used in the present application mean that the elements or objects before the words cover the elements or objects listed after the words and their equivalents, without excluding other elements or objects.

[0019] In one aspect, the present application provides a nano-enzyme composite microneedle patch for treating acne, comprising a microneedle body and a microneedle backing connected, the microneedle body is made of γ-polyglutamic acid, and the microneedle body is loaded with sound-sensitive nanoparticles with enzyme-like properties, the sound-sensitive nanoparticles with enzyme-like properties are manganese porphyrin metal organic frameworks (PCN222-Mn).

[0020] When the present application is used, the PCN222-Mn nano-enzyme released by the nano-enzyme composite microneedle patch penetrating the epidermis can produce singlet oxygen under ultrasonic conditions, and can convert the inflammatory reactive oxygen species (including superoxide anion and hydrogen peroxide) in the pathological microenvironment of acne into oxygen, the oxygen produced in situ provides sufficient raw materials for sonodynamic therapy and further realizes efficient killing of propionibacterium acnes, on the other hand, it can improve the hypoxic microenvironment of acne and effectively promote the tissue repair of the acne site; the related antigens released by the death of the bacteria after sonodynamic therapy, in cooperation with PCN222-Mn and γ-PGA dissolved after the tip of the needle, promote the maturation of DCs, the mature DCs present bacterial antigens, realize antibacterial immune response, form immune memory, and prevent secondary bacterial infection.

[0021] In one specific embodiment, the length of the tip of the nano-enzyme composite microneedle patch is 300-650 μm.

[0022] In one specific embodiment, the microneedle backing is made of biodegradable material. Alternatively, the biodegradable material is any one or more of polyvinyl alcohol, gelatin, hyaluronic acid, and polyvinylpyrrolidone. It should be noted that the microneedle backing is mainly used to fix the microneedle body and adhere to the skin, and the material thereof mainly considers the adhesion, flexibility and non-sensitization to the skin. The materials in the above embodiments are only preferred materials of the present application, and other backing materials suitable for living organisms in the prior art can also be applicable to the present application.

[0023] On the other hand, the present application also provides a preparation method of the nano-enzyme composite microneedle patch for treating acne described in any one of the above, comprising the following steps: S1: preparing sound-sensitive nanoparticles with enzyme-like properties; S2: dissolve the microneedle backing material and the gamma-polyglutamic acid in solvent one respectively, stir until completely dissolved, to obtain a microneedle backing pre-gel solution and a gamma-polyglutamic acid pre-gel solution; S3: uniformly disperse the enzyme-like sound-sensitive nanoparticles in the gamma-polyglutamic acid pre-gel solution, then add the mixed solution into the microneedle mold, and dry to obtain a microneedle mold filled with microneedle bodies; S4: add the microneedle backing pre-gel solution into the microneedle mold filled with microneedle bodies, dry and demold to obtain the nano-enzyme composite microneedle patch.

[0024] In a specific embodiment, when the enzyme-like sound-sensitive nanoparticles are manganese porphyrin metal organic frameworks, step S1 specifically comprises the following substeps: dissolve tetracarboxylic tetraphenyl manganese porphyrin, benzoic acid and zirconyl chloride octahydrate in solvent two, then stir at 80-100°C and in the dark for 4-7h to obtain the enzyme-like sound-sensitive nanoparticles.

[0025] It should be noted that the manganese porphyrin metal organic framework is a nanostructure constructed by manganese metal ions and porphyrin ligands, which is a prior art; the preparation method of the above embodiment is only one preferred preparation method of the present application, and other methods capable of preparing manganese porphyrin metal organic frameworks in the prior art can also be applied to the present application.

[0026] In a specific embodiment, in step S2, the mass fraction of the solute in the microneedle backing pre-gel solution is 10-40%, and the mass fraction of the solute in the gamma-polyglutamic acid pre-gel solution is 10-60%.

[0027] In a specific embodiment, in step S3, the concentration of the enzyme-like sound-sensitive nanoparticles in the gamma-polyglutamic acid pre-gel solution is 10-100 μg / mL.

[0028] Embodiment 1 A nano-enzyme composite microneedle patch for treating acne is prepared by the following steps: (1) dissolve 20 mg of sound-sensitive agent tetracarboxylic tetraphenyl manganese porphyrin, 580 mg of benzoic acid and 60 mg of zirconyl chloride octahydrate in 20 mL of N,N-dimethylformamide, stir at 90°C and in the dark for 5h to obtain PCN222-Mn nanoparticles; (2) 1.5 g PVA was dissolved in 10 mL deionized water, 1.2 g γ-PGA was dissolved in 2 mL deionized water, and the PVA pre-gel solution and the γ-PGA pre-gel solution were obtained by stirring at room temperature until completely dissolved, and the PCN222-Mn nanoparticles were uniformly dispersed in the γ-PGA pre-gel solution, wherein the concentration of the nanoparticles was 50 μg / mL; (3) The γ-PGA pre-gel solution with dispersed nanoparticles was dropped onto the polydimethylsiloxane microneedle mold, then placed in a vacuum drying oven, vacuumed for 15 min, removed, and the bubbles in the mold were removed by again dropping the γ-PGA pre-gel solution with dispersed nanoparticles, again placing in the vacuum drying oven and vacuuming for 15 min, removing the excess liquid containing bubbles on the mold, then dropping the PVA pre-gel solution, and then placing the mold in a constant temperature drying oven at 25 °C for 24 h, and then demolding to obtain a nanose enzyme composite microneedle patch.

[0029] Example 2 Different from Example 1, the concentration of the nanoparticles in step (2) of this example was 25 μg / mL.

[0030] Example 3 Different from Example 1, the concentration of the nanoparticles in step (2) of this example was 100 μg / mL.

[0031] Comparative Example 1 Different from Example 1, this comparative example did not include step (1), and the PCN222-Mn nanoparticles were not added in step (2).

[0032] Test Example 1 The morphology of the PCN222-Mn nanoparticles of Example 1 was observed by scanning electron microscopy and transmission electron microscopy, and the results are shown in Figure 1 From Figure 1 it can be seen that the PCN222-Mn nanoparticles prepared in Example 1 have uniform particle size, regular morphology, are shuttle-shaped, and have good dispersibility.

[0033] Test Example 2 The catalytic hydrogen peroxide oxygen production of PCN222-Mn nanoparticles of different concentrations was tested, and the results are shown in Figure 2 From Figure 2 it can be seen that within 10 min, the oxygen production of the nanoparticles catalyzing hydrogen peroxide gradually increased, and the higher the concentration of the PCN222-Mn nanoparticles, the higher the oxygen production, which had a certain concentration dependence; there are a large number of hydrogen peroxide in the acne inflammatory microenvironment, and the PCN222-Mn nanoparticles can convert them into oxygen to improve the anaerobic microenvironment of acne.

[0034] Test Example 3 The sonodynamic properties of PCN222-Mn nanoparticles were tested under five experimental conditions: ultrasonic treatment of aqueous solution alone (US), aqueous solution of PCN222-Mn nanoparticles alone (PCN222-Mn), aqueous solution of PCN222-Mn nanoparticles with hydrogen peroxide added (PCN222-Mn+H2O2), ultrasonic treatment of aqueous solution of PCN222-Mn nanoparticles alone (PCN222-Mn+US), and ultrasonic treatment of aqueous solution of PCN222-Mn nanoparticles with hydrogen peroxide added (PCN222-Mn+US+H2O2). The electron spin resonance spectra (ESR) of singlet oxygen generated under different conditions were as follows: Figure 3 As shown. Figure 3 It can be seen that no spectral peaks appeared under the conditions of ultrasound alone, nanoparticles alone, and nanoparticles alone plus hydrogen peroxide, proving that no singlet oxygen was produced; the singlet oxygen triple characteristic peak (1:1:1) appeared in the ESR spectrum of ultrasonic treatment under the conditions of nanoparticles plus ultrasound and nanoparticles plus hydrogen peroxide, proving that PCN222-Mn nanoparticles are a highly efficient sonosensitive material; in addition, since nanoparticles can catalyze the conversion of hydrogen peroxide into oxygen, providing raw materials for the sonodynamic generation of singlet oxygen, the ESR peak of ultrasonic treatment under the conditions of nanoparticles plus hydrogen peroxide is more intense than the ESR peak of nanoparticles plus ultrasound.

[0035] Test Example 4 The morphology of the nanozyme composite microneedle patch prepared in each example was observed using a fluorescence microscope and a scanning electron microscope. The morphology of Example 1 is shown in FIG. Figure 4 As shown. Figure 4 It can be seen that the composite microneedle patch loaded with PCN222-Mn nanoparticles can be observed to have a uniform red fluorescence signal in the microneedle tip structure in the rhodamine channel of the fluorescence microscope, while the backing is not loaded with nanoparticles and is pure PVA material, so no fluorescence signal is observed, proving that the nanoparticles are evenly wrapped in the needle tip and the microneedle tip morphology structure is complete, with a needle tip length of 650 μm and a bottom diameter of 300 μm.

[0036] Test Example 5 The transdermal performance and solubility of the nanozyme composite microneedle patch of the present invention were tested. In order to facilitate observation, a composite microneedle patch loaded with methylene blue dye was prepared. The results are as follows Figure 5 As shown. Figure 5It can be seen that before piercing the pig skin, the microneedle tip showed a complete needle tip morphology. When the microneedle was removed 2 minutes after piercing the pig skin, it was observed that visible micropores were formed on the pig skin, proving that the microneedle can effectively penetrate the epidermal stratum corneum barrier. After piercing the pig skin, the microneedle tip structure disappeared, proving that the microneedle tip was completely dissolved and could release nanoparticles.

[0037] Test Example 6 The antibacterial properties of the composite microneedle patch against Propionibacterium acnes were tested under different conditions: bacterial suspension alone (Control) without ultrasound (US-) or with ultrasound (US+), composite microneedle plus bacterial suspension alone (PMMNs), and composite microneedle plus bacterial suspension with hydrogen peroxide added (PMMNs+H2O2). Figure 6 As shown. Figure 6 It can be seen that without ultrasonic treatment and in the absence of hydrogen peroxide, the composite microneedles have a very weak antibacterial effect; without ultrasonic treatment and in the presence of hydrogen peroxide, the antibacterial rate of the composite microneedles is slightly improved; when subjected to ultrasonic treatment alone, the antibacterial efficiency is low; when the composite microneedles are subjected to ultrasonic treatment, the antibacterial efficiency is greatly improved, and in the presence of hydrogen peroxide, the antibacterial rate is close to 100%, proving that the composite microneedles have good sonodynamic antibacterial properties.

[0038] Test Example 7 In order to prove that PCN222-Mn can promote DCs maturation by synergizing with γ-PGA dissolved by needle tip and effectively activating and promoting DCs maturation after ultrasound treatment, the DCs maturation rate was detected by flow cytometry using DCs maturation markers (CD11c+ / CD86+ / CD80+). Figure 7 As shown. Figure 7 As can be seen, compared to the control group, the DC maturation rate in the MNs group (i.e., the blank microneedle group, microneedles without nanoparticles) showed a slight increase, while the DC maturation rate in the PMMNs group (i.e., the nanoparticle-loaded composite microneedle group) showed a slight increase. This may be because the Mn2+ released by γ-PGA and PCN222-Mn nanozymes promotes DC maturation. Furthermore, after sonodynamic therapy (i.e., the PMMNs+SDT group), the DC maturation rate was significantly increased, approximately four times that of the control group. This suggests that PMMNs can act as an adjuvant to stimulate DC activation and maturation, and synergize with bacterial antigens released by P. acnes after ultrasound treatment to effectively promote DC maturation. As the most powerful antigen-presenting cells, DCs play a key role in bridging innate and adaptive immunity. Mature DCs have longer dendrites and express higher levels of co-stimulatory molecules than immature DCs, demonstrating enhanced antigen presentation.

[0039] Test Example 8 The in vivo therapeutic effect of the nano-enzyme composite microneedle patch was tested, and the in vivo animal experiment of treating mouse acne by using the nano-enzyme composite microneedle patch was used to verify. The mouse acne animal model was established by intradermal injection of P. acnes on the back skin of the mouse, and the mouse acne was treated according to the following methods: without any treatment (G1), using erythromycin ointment treatment (G2), using blank microneedle for ultrasonic treatment (G3), using composite microneedle treatment (G4), and using composite microneedle ultrasonic treatment (G5). The thickness of the mouse acne in each group was measured and counted every day, and the results are shown in Figure 8 As can be seen from Figure 8 , the thickness of the mouse acne in the G1 group without any treatment increased over time, and the same trend was observed in the G2 group treated with erythromycin ointment, the G3 group treated with ultrasonic treatment after blank microneedle, and the G4 group treated with composite microneedle patch without ultrasonic treatment. In contrast, the thickness of the mouse acne in the G5 group treated with ultrasonic treatment after using the nano-enzyme composite microneedle patch with sonodynamic effect showed the opposite trend. The transdermal treatment of the composite microneedle can improve the hypoxic microenvironment and generate singlet oxygen under ultrasonic stimulation, killing P. acnes and reducing the thickness of the mouse acne over time.

[0040] Test Example 9 The expression of peripheral blood memory B cells was investigated by flow cytometry after secondary infection of P. acnes, and the results are shown in Figure 9 As can be seen from Figure 9 , compared with other groups, the G5 group treated with ultrasonic treatment after nano-enzyme composite microneedle patch had a higher expression level of memory B cells (CD45+ / CD19+ / CD38−) (G1 group 14.1%, G2 group 14.4%, G3 group 15.5%, G4 group 18.9%, G5 group 28.5%), indicating that immune memory effect may be induced after treatment. In addition, higher lgG antibody levels were detected in the serum of the G5 group compared with other groups, indicating that more intense humoral immune response can be achieved after ultrasonic treatment with nano-enzyme composite microneedle patch, proving that the nano-enzyme composite microneedle patch can be used as an adjuvant sonosensitizer material to induce immune memory by causing bacterial immunogenic death of P. acnes.

[0041] Test Example 10 After treatment of different groups, the anti-acne secondary recurrence performance of the nano-enzyme composite microneedle patch was tested. The thickness of the mouse acne after secondary infection of P. acnes was counted, and the results are shown in Figure 10 As can be seen from Figure 10 , compared with the thickness of the mouse acne in the G1-G4 groups, the thickness of the mouse acne in the G5 group treated with ultrasonic treatment after using the nano-enzyme composite microneedle patch with sonodynamic effect was significantly smaller, showing the effect of preventing acne recurrence.

[0042] In summary, the nano-enzyme composite microneedle patch has a transdermal treatment and recurrence prevention effect on acne; the composite microneedle patch is composed of a gamma-PGA microneedle body and a PVA backing, and the tip of the microneedle patch is loaded with enzyme-like sound-sensitive nanoparticles PCN222-Mn; the composite microneedle patch can penetrate the epidermis to reach the acne lesion site and quickly dissolve and release the nanoparticles; the nanoparticles can convert harmful reactive oxygen in the acne inflammatory microenvironment into oxygen, enhance the sonodynamic therapy and improve the hypoxic microenvironment of acne, and effectively promote the healing of acne and prevent secondary recurrence. Compared with the prior art, the present application has significant progress.

[0043] The above is only a representative embodiment of the present application, and does not limit the present application in any form. Any skilled person in the art can make some minor changes or modifications to the above disclosed technical content without departing from the scope of the technical solution of the present application, and such embodiments are equivalent embodiments of the present application. Any simple modification, equivalent change and modification of the above embodiments made according to the technical essence of the present application, without departing from the technical solution of the present application, are still within the scope of the technical solution of the present application.

Claims

1. A nanozyme composite microneedle patch for treating acne, comprising a connected microneedle body and a microneedle backing, characterized in that: The microneedle body is made of gamma-polyglutamic acid, and the microneedle body is loaded with sonogenic nanoparticles with enzyme-like properties.

2. The nanozyme composite microneedle patch for treating acne according to claim 1, characterized in that: The needle tip length of the nanozyme composite microneedle patch is 300-650 μm.

3. The nanozyme composite microneedle patch for treating acne according to claim 1, characterized in that: The microneedle backing is made of biodegradable material.

4. The nanozyme composite microneedle patch for treating acne according to claim 3, characterized in that: The biodegradable material is any one or more of polyvinyl alcohol, gelatin, hyaluronic acid, and polyvinyl pyrrolidone.

5. The nanozyme composite microneedle patch for treating acne according to any one of claims 1 to 4, characterized in that: The sonosensitive nanoparticles with enzyme-like properties are manganese porphyrin metal organic frameworks.

6. The method for preparing the nanozyme composite microneedle patch for treating acne according to any one of claims 1 to 5, characterized in that: The following steps are involved: S1: Preparation of sonogenic nanoparticles with enzyme-like properties; S2: dissolving the microneedle backing material and γ-polyglutamic acid in solvent 1 respectively, stirring until completely dissolved, to obtain a microneedle backing pregel solution and a γ-polyglutamic acid pregel solution; S3: uniformly dispersing the sonogenic nanoparticles having enzyme-like properties in the γ-polyglutamic acid pregel solution, then adding the mixed solution into a microneedle mold, and drying to obtain a microneedle mold filled with microneedle bodies; S4: adding the microneedle backing pre-gel solution into the microneedle mold filled with microneedle bodies, drying, and demoulding to obtain the nanozyme composite microneedle patch.

7. The method for preparing the nanozyme composite microneedle patch for treating acne according to claim 6, characterized in that: When the sonosensitive nanoparticles with enzyme-like properties are manganese porphyrin metal-organic frameworks, step S1 specifically includes the following sub-steps: dissolving tetracarboxytetraphenylmanganese porphyrin, benzoic acid and zirconyl chloride octahydrate in solvent 2, and then stirring at 80-100° C. and in the dark for 4-7 hours to obtain the sonosensitive nanoparticles with enzyme-like properties.

8. The method for preparing the nanozyme composite microneedle patch for treating acne according to claim 6, characterized in that: In step S2, the mass fraction of the solute in the microneedle backing pregel solution is 10-40%, and the mass fraction of the solute in the γ-polyglutamic acid pregel solution is 10-60%.

9. The method for preparing the nanozyme composite microneedle patch for treating acne according to any one of claims 6 to 8, characterized in that: In step S3, the concentration of the sonosensitizing nanoparticles with enzyme-like properties in the γ-polyglutamic acid pregel solution is 10-100 μg / mL.

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