Glucose-responsive cascade antibacterial nanomaterial and preparation method and application thereof

Abstract

The application relates to the technical field of biomedical materials, and discloses a glucose-responsive cascade antibacterial nanomaterial as well as a preparation method and application thereof. The nanomaterial takes metal Mn-doped Prussian blue as a core, is loaded with gold nanoparticles on the surface, and is wrapped with a chitosan outer layer. The glucose-oxidase-like activity of the gold nanoparticles is utilized to specifically respond to a high-glucose environment at a diabetic wound, and hydrogen peroxide is generated through catalysis; then, the Mn-doped Prussian blue plays a peroxidase-like role to catalyze the hydrogen peroxide into highly toxic hydroxyl radicals, so that efficient killing of bacteria is realized; meanwhile, the material also has a photothermal effect, and can realize synergistic sterilization. The material can intelligently start a cascade reaction by using a microenvironment of a lesion, efficiently and accurately treat bacterial infection, and promote wound healing.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, and in particular to a glucose-responsive cascade antibacterial nanomaterial, its preparation method, and its application. Background Technology

[0002] Diabetic wound infections, particularly diabetic foot ulcers, are among the most serious and common complications of diabetes, and their treatment remains a significant clinical challenge. Currently, diabetic skin wounds, due to their high glucose concentration and low pH microenvironment, are prone to bacterial infection and other inflammatory responses, leading to slow-healing chronic wound infections. However, traditional antibiotic treatments can result in the development of multidrug-resistant bacteria. Therefore, developing new treatment strategies is urgently needed to effectively address bacterial infections and inflammation in chronic wounds.

[0003] In recent years, novel therapies such as photothermal therapy (PTT) and chemodynamic therapy (CDT) have shown great potential. Photothermal therapy utilizes photothermal agents to convert light energy into heat energy under near-infrared light irradiation, physically disrupting bacterial biofilms through localized high temperatures, offering advantages such as rapid onset and broad-spectrum bactericidal activity. Chemodynamic therapy, on the other hand, converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals through Fenton or Fenton-like reactions, achieving specific bactericidal effects and reducing the likelihood of inducing drug resistance. However, these novel therapies still have limitations: photothermal therapy has limited tissue penetration depth, while the efficacy of chemodynamic therapy is limited by insufficient endogenous H2O2 in the microenvironment of diabetic wounds.

[0004] It is worth noting that the study found that gold nanoparticles can mimic the function of glucose oxidase, effectively catalyzing the oxidation reaction of glucose and continuously generating H2O2 and gluconic acid. This process cleverly transforms the pathogenic factor (high sugar) into a therapeutic advantage and provides "fuel" for chemodynamic therapy.

[0005] Therefore, developing a nanomaterial that can intelligently respond to the high-sugar microenvironment of diabetic wounds, self-supply H2O2, and achieve combined PTT / CDT antibacterial activity has significant clinical implications and application value. Summary of the Invention

[0006] To overcome the difficulties currently encountered in the treatment of diabetic wounds, the present invention aims to provide a method for preparing a glucose-responsive cascade antibacterial nanomaterial (PMn-Au@CTS) that promotes diabetic wound healing, and its application. The glucose-responsive cascade antibacterial nanomaterial constructed in this invention can self-produce H2O2 and achieves combined PTT / CDT antibacterial action. This overcomes the shortcomings of single-therapy antibacterial treatment, enabling better antibacterial effects and fewer side effects with lower drug doses.

[0007] The technical solution of this invention is as follows: Firstly, for product solutions A glucose-responsive cascade antibacterial nanomaterial, wherein the nanomaterial has a core-shell structure, comprising a Mn-doped Prussian blue core, wherein the core is cubic in shape and has a particle size of 150–160 nm. Gold nanoparticles loaded on the surface of the core; and a chitosan layer wrapped around the outermost layer; The overall particle size of the antibacterial nanomaterial is 190–210 nm.

[0008] As a preferred technical solution, the gold nanoparticles are chemically bonded and anchored to the surface of the Prussian blue core via in-situ reduction.

[0009] Secondly, regarding the methodology and solutions. This invention provides a method for preparing glucose-responsive cascade antibacterial nanomaterials, comprising the following steps: S1 and PMn synthesis: A solvothermal method was used to add a manganese source solution dropwise into a potassium ferricyanide solution and react under acidic conditions at 80°C. After centrifugation, washing, and drying, Mn-doped Prussian blue cores (PMn for short) were obtained. S2, PMn-Au synthesis: PMn is dispersed in water, chloroauric acid is added, and after stirring in the dark, sodium borohydride is added to carry out an in-situ reduction reaction, so that gold nanoparticles grow in situ on the surface of PMn. The reaction product is centrifuged, washed and dried to obtain PMn-Au loaded with gold nanoparticles. S3, PMn-Au@CTS Synthesis: PMn-Au solution was added dropwise to chitosan solution, stirred to fully encapsulate the chitosan, and then centrifuged, washed, and dried to obtain the final product PMn-Au@CTS.

[0010] As a preferred technical solution, in step S1, the reaction temperature of the solvothermal method is 80°C and the reaction time is 20 h.

[0011] As a preferred technical solution, in step S1, the concentrations of both potassium ferricyanide and manganese source are 2 mmol / L; the acidic condition is adjusted by hydrochloric acid, and the concentration of hydrochloric acid is 0.01 mol / L.

[0012] As a preferred technical solution, in step S2, the mass ratio of PMn, chloroauric acid and sodium borohydride is 10:10:11.35.

[0013] As a preferred technical solution, in step S2, gold nanoparticles are chemically bonded and anchored to the PMn surface, resulting in a uniform and firm load.

[0014] As a preferred technical solution, in step S3, the mass ratio of PMn-Au to chitosan is 1:1.

[0015] Thirdly, application solutions The present invention also provides the application of glucose-responsive cascade antibacterial nanomaterials in the preparation of drugs that promote the healing of diabetic wounds.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The glucose-responsive cascade antibacterial nanomaterial PMn-Au@CTS prepared in this invention has a combined rapid bactericidal effect based on photothermal therapy (PTT) and chemokinetic therapy (CDT). Experiments show that PMn-Au@CTS at a concentration of 150 μg / mL, after irradiation with 808 nm infrared light for 5 min, can kill 99.9% of Staphylococcus aureus and Escherichia coli; at a concentration of 200 μg / mL, the inhibition rate against methicillin-resistant Staphylococcus aureus (MRSA) can also reach 99.9%.

[0017] (2) The glucose-responsive cascade antibacterial nanomaterial PMn-Au@CTS prepared in this invention can continuously catalyze the decomposition of glucose to produce gluconic acid and hydrogen peroxide. On the one hand, it alleviates the high-sugar microenvironment in diabetic wounds, and on the other hand, it provides hydrogen peroxide substrate for chemokinetic therapy (CDT), realizing the cascade catalysis of self-supplied H2O2.

[0018] (3) The outer chitosan of the glucose-responsive cascade antibacterial nanomaterial PMn-Au@CTS prepared in this invention can be protonated and flipped to a positive charge in the acidic microenvironment (pH 5.5-6.5) of diabetic wounds, thereby binding with negatively charged bacteria on the surface through electrostatic interaction, further enhancing the antibacterial effect.

[0019] (4) The preparation method of the present invention (solvent thermal method + in-situ reduction method + chitosan coating) is simple, efficient, and mild, suitable for large-scale industrial application and promotion, and meets the requirements of environmental friendliness. Attached Figure Description

[0020] Figure 1 This is a comparison of the photothermal heating curves of PB and PMn prepared in Example 1; Figure 2 These are scanning electron microscope (SEM) images of PMn, PMn-Au, and PMn-Au@CTS nanoparticles prepared in Example 1; Figure 3 These are transmission electron microscopy (TEM) images of PMn, PMn-Au, and PMn-Au@CTS nanoparticles prepared in Example 1; Figure 4The X-ray diffraction (XRD) patterns of PMn, PMn-Au, and PMn-Au@CTS nanoparticles prepared in Example 1 are shown. Figure 5 These are the X-ray photoelectron spectroscopy (XPS) spectra of PMn, PMn-Au, and PMn-Au@CTS nanoparticles prepared in Example 1; Figure 6 This is a photothermal heating curve of PMn-Au@CTS nanoparticles prepared in Example 1 at different concentrations; Figure 7 This is a photothermal cycling stability test diagram of PMn-Au@CTS nanoparticles prepared in Example 1; Figure 8 This is a graph showing the performance of PMn-Au@CTS nanoparticles prepared in Example 1 in catalyzing the generation of ·OH at different concentrations (652 nm absorbance). Figure 9 This is a graph showing the in vitro antibacterial activity (colony plate photo) of PMn-Au@CTS nanoparticles prepared in Example 1 against different bacteria. Figure 10 This is a comparison chart of the antibacterial properties of different materials (Control, Glu, PMn, PMn-Au, PMn-Au@CTS, PMn-Au@CTS+NIR) prepared in Example 1 against various bacteria; Figure 11 This is a graph showing the in vitro hemolytic activity test results of the PMn-Au@CTS nanoparticles prepared in Example 1; Figure 12 This is a graph showing the effect of PMn-Au@CTS nanoparticles prepared in Example 1 on the cell viability of NIH-3T3 cells and HUVEC cells (CCK-8 assay). Detailed Implementation

[0021] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below with reference to specific embodiments.

[0022] Example 1 I. Preparation of PMn-Au@CTS Nanomaterials This embodiment provides a method for preparing glucose-responsive cascade antibacterial nanomaterials (PMn-Au@CTS), specifically including the following steps: Synthesis of S1 and PMn (Mn-doped Prussian blue core): Weigh out K4[Fe(CN)6] (33.79 mg, 0.08 mmol) and polyvinylpyrrolidone (PVP, 3.05 g) and dissolve them in deionized water (40 mL). The resulting solution is liquid A. Liquid B was prepared by adding MnSO4·H2O (13.52 mg, 0.08 mmol) and PVP (3.05 g) to deionized water (40 mL).

[0023] Liquid B was added dropwise to liquid A under magnetic stirring and stirred for 10 min. Then, HCl solution (80 mL, 0.01 M) was added and stirred for another 10 min. The resulting mixture was transferred to a PTFE-lined stainless steel autoclave and heated at 80 °C for 20 h.

[0024] After the reaction was completed, the product was naturally cooled to room temperature, centrifuged at 11,000 rpm for 10 min, washed twice with deionized water and anhydrous ethanol, and finally freeze-dried under vacuum for 12 h to obtain PMn.

[0025] Comparison with the synthesis of sample PB (undoped Prussian blue): Following the same method described above, without adding MnSO4·H2O, undoped Prussian blue (PB) was prepared for subsequent comparative experiments.

[0026] Synthesis of S2 and PMn-Au (supported gold nanoparticles): Weigh 10 mg of PMn obtained in step S1 and ultrasonically disperse it in 10 mL of deionized water to form a homogeneous dispersion. Add 10 mg of HAuCl4 under light-protected conditions and stir in an ice bath for 2 h. Then, with vigorous stirring, freshly prepared NaBH4 (11.35 mg) in cold water was added quickly in one go, and stirring continued for 3 hours; After the reaction was completed, the product was centrifuged at 11,000 rpm for 5 min, the supernatant was discarded, the precipitate was washed three times with deionized water, and finally freeze-dried under vacuum for 12 h to obtain PMn-Au.

[0027] Synthesis of S3, PMn-Au@CTS (chitosan coating): Weigh 10 mg of PMn-Au obtained in step S2 and ultrasonically disperse it in 2 mL of deionized water to obtain PMn-Au solution.

[0028] Alternatively, dissolve 10 mg of chitosan in 5 mL of deionized water and stir until completely dissolved to obtain a chitosan solution.

[0029] PMn-Au solution was added dropwise to chitosan solution with stirring at room temperature. After the addition was complete, stirring was continued at room temperature for 24 h. After the reaction was completed, the product was centrifuged (11000 rpm, 10 min), the supernatant was discarded, the precipitate was washed three times with deionized water, and finally freeze-dried under vacuum for 12 h to obtain PMn-Au@CTS.

[0030] II. Material Characterization and Performance Testing 1. Comparison of photothermal heating performance of PB and PMn The PB and PMn nanoparticles prepared above were ultrasonically dispersed separately in deionized water to prepare a dispersion with a concentration of 100 μg / mL. 1 mL of the dispersion was added to an EP tube and tested with an 808 nm near-infrared laser (power density 1.0 W / cm²). 2 Irradiate for 10 minutes. Use an electronic thermometer to measure and record the temperature every 30 seconds.

[0031] The results are as follows Figure 1 As shown, both PB and PMn exhibit a significant heating trend under laser irradiation. PMn shows significantly better photothermal heating performance than PB, indicating that manganese ion doping can effectively optimize the photothermal performance of Prussian blue.

[0032] 2. Morphological characterization of PMn, PMn-Au and PMn-Au@CTS nanoparticles (SEM and TEM) PMn, PMn-Au and PMn-Au@CTS powders from Example 1 were ultrasonically dispersed in anhydrous ethanol, dropped onto a silicon wafer and allowed to dry naturally. After gold sputtering, the morphology was observed using a scanning electron microscope.

[0033] The results are as follows Figure 2 As shown, PMn exhibits a regular cubic morphology with a smooth surface. After loading Au nanoparticles, the surface of PMn-Au becomes rough, and a large number of fine particles are visible uniformly distributed on the cubic surface. After further coating with chitosan, the particle size of PMn-Au@CTS increases, and the shape becomes more of a square sphere.

[0034] The PMn, PMn-Au, and PMn-Au@CTS powders from Example 1 were ultrasonically dispersed in anhydrous ethanol, dropped onto a copper grid and allowed to dry naturally. The internal structure was then observed using a transmission electron microscope.

[0035] The results are as follows Figure 3 As shown, Au nanoparticles are in situ loaded onto the surface of PMn nanoparticles.

[0036] 3. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis The PMn, PMn-Au, and PMn-Au@CTS powders from Example 1 were subjected to phase analysis using an X-ray diffractometer.

[0037] The results are as follows Figure 4As shown in the figure, the XRD pattern of PMn shows diffraction peaks belonging to Prussian blue in the range of 10° to 85°, indicating that PMn was successfully prepared. In the XRD pattern of PMn-Au, in addition to the characteristic peaks of Prussian blue, diffraction peaks belonging to Au nanoparticles appear in the range of 35° to 90°, indicating that Au nanoparticles were successfully grown on the PMn surface. The diffraction peak intensity of PMn-Au@CTS is somewhat weakened.

[0038] The PMn, PMn-Au, and PMn-Au@CTS powders from Example 1 were used for elemental composition and chemical state analysis using X-ray photoelectron spectroscopy.

[0039] The results are as follows Figure 5 As shown, PMn mainly contains Fe, Mn, C, N, and O elements, indicating that PMn was successfully prepared. The presence of additional Au signal peaks in PMn-Au indicates that Au nanoparticles were successfully grown on the PMn surface. The elemental composition of PMn-Au@CTS is basically the same as that of PMn-Au, indicating that chitosan coating does not change the core chemical composition.

[0040] 4. Photothermal performance and photothermal stability testing PMn-Au@CTS from Example 1 was ultrasonically dispersed in deionized water to prepare dispersions of different concentrations (0, 50, 100, 150, 200 μg / mL). 1 mL of the dispersion was added to an EP tube and tested with an 808 nm near-infrared laser (1.0 W / cm²). 2 Irradiate for 10 minutes, and use an electronic thermometer to measure and record the temperature every 30 seconds.

[0041] The results are as follows Figure 6 As shown in the figure, the control group (0 μg / mL) showed no significant temperature change under laser irradiation. With increasing PMn-Au@CTS concentration, the photothermal heating effect gradually increased; the temperature of the 200 μg / mL group rose from 26.6℃ to 61.0℃ after 10 min of irradiation, indicating that PMn-Au@CTS has good photothermal conversion performance.

[0042] The above 150 μg / mL dispersion was subjected to an 808 nm laser (1.0 W / cm²) 2 Five on / off cycle tests were performed, and the temperature was measured and recorded every 30 seconds using an electronic thermometer. In each cycle, the laser was turned on for 10 minutes and then turned off for 10 minutes to cool down.

[0043] The results are as follows Figure 7As shown, PMn-Au@CTS rapidly heated to approximately 55°C after each laser activation during 5 cycles, and quickly cooled to room temperature after the laser was turned off. The maximum temperature remained essentially consistent across the 5 cycles, without significant attenuation, indicating that PMn-Au@CTS possesses excellent photothermal stability.

[0044] 5. Testing of glucose-responsive cascade properties of PMn-Au@CTS nanoparticles Au in PMn-Au@CTS can use glucose as a substrate, oxidizing and decomposing it to produce gluconic acid and H2O2. Under acidic conditions, Fe in PMn-Au@CTS... 2+ and Mn 2+ The catalytic generation of hydroxyl radicals ·OH from H2O2 was achieved through a Fenton-like reaction. ·OH can react with 3,3',5,5'-tetramethylbenzidine (TMB) to generate TMB oxide. The TMB oxide product has a characteristic peak at 652 nm. The performance of its glucose-responsive cascade was evaluated by measuring the absorbance at 652 nm using a UV spectrophotometer.

[0045] Different concentrations of PMn-Au@CTS (0, 25, 50, 100, 200 μg / mL) were added to PBS buffer (pH 4.6) containing glucose solution (5 mg / mL, 50 μL) and TMB (5 mg / mL, 50 μL), and reacted in the dark for 10 min. The precipitate was then removed by centrifugation, and the absorbance of the supernatant at 652 nm was measured using a UV spectrophotometer.

[0046] The results are as follows Figure 8 As shown, under pH 4.6 conditions, the peak value at 652 nm increases with increasing drug concentration, indicating that PMn-Au@CTS nanomaterials can undergo glucose oxidase-like activity and Fenton-like reaction to generate ·OH in an acidic microenvironment.

[0047] 6. In vitro antibacterial performance testing and comparison of antibacterial performance of different materials Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA) were selected as model strains.

[0048] Dilute the fresh bacterial suspension to 1×10⁻⁶ 6 CFU / mL. Different concentrations of PMn-Au@CTS (0, 50, 100, 150, 200 μg / mL) were mixed with an equal volume of bacterial suspension and incubated at 37°C for 5 min. The mixture was divided into two groups: one group was irradiated with laser (808 nm, 1.0 W / cm²). 2The treatment consisted of two groups: a control group (5 min) and a control group without laser irradiation. After treatment, the cells were serially diluted 10-fold with PBS, and 100 μL of each group was spread onto LB agar plates and incubated overnight at 37°C. The number of colonies was then counted.

[0049] The results are as follows Figure 9 As shown in the figure, at the same concentration, the number of bacterial colonies in the near-infrared treatment group was significantly lower than that in the non-near-infrared treatment group. With increasing PMn-Au@CTS concentration, the number of bacterial colonies decreased significantly. At a concentration of 150 μg / mL, PMn-Au@CTS achieved an inhibition rate of 99.9% against *S. aureus* and *E. coli*; for MRSA, 200 μg / mL PMn-Au@CTS achieved a similar inhibition rate.

[0050] The following experimental groups were set up: Control (PBS), Glu (glucose), PMn, PMn-Au, and PMn-Au@CTS. *S. aureus*, *E. coli*, and MRSA were used as test strains, with a bacterial suspension concentration of 1×10⁻⁶. 6 CFU / mL, processed in the same way as the antibacterial test described above.

[0051] The results are as follows Figure 10 As shown in the figure, the Control and Glu groups showed no significant antibacterial activity against any of the three strains. The PMn group exhibited low antibacterial activity. The PMn-Au group showed significantly enhanced antibacterial activity, indicating the importance of Au oxidizing glucose to provide H2O2 for chemokinetic therapy. The PMn-Au@CTS group showed the best antibacterial effect, with an inhibition rate of 99.9%, demonstrating that chitosan can enable PMn-Au@CTS to electrostatically bind to bacteria, thereby enhancing its antibacterial effect.

[0052] 7. Hemolytic test Fresh defibrinated sheep blood was washed with physiological saline and centrifuged three times to obtain purified red blood cells. A 10% red blood cell suspension was prepared with physiological saline.

[0053] The following groups were set up: positive control group (50 μL red blood cells + 950 μL distilled water), negative control group (50 μL red blood cells + 950 μL physiological saline), and experimental group (50 μL red blood cells + 950 μL physiological saline solutions of different concentrations of PMn-Au@CTS, with final concentrations of 50, 100, 150, 200, and 300 μg / mL, respectively). After co-culturing at 37℃ for 1.5 h, the mixture was centrifuged at 2500 rpm for 5 min, and the OD value of the supernatant was measured at 540 nm using an EnSpire, PerkinElmer microplate reader.

[0054] The results are as follows Figure 11As shown, when the concentration was increased to 300 μg / mL, the hemolysis rate of PMn-Au@CTS was still lower than the international standard requirement (5%), indicating that the material did not exhibit significant hemolysis and had good biocompatibility.

[0055] 8. In vitro cytotoxicity test The cytotoxicity of PMn-Au@CTS against mouse embryonic fibroblasts (NIH-3T3) and human umbilical vein endothelial cells (HUVEC) was evaluated using the CCK-8 assay.

[0056] Cells were seeded in 96-well plates (1 × 10⁶ cells per well). 5 Cells were cultured in a 5% CO2 incubator at 37°C for 24 h. The culture medium was discarded, and fresh culture medium containing different concentrations of PMn-Au@CTS (0, 50, 100, 150, 200, 300 μg / mL) was added. Cultures were continued for 24 h and 72 h, respectively. After treatment, the cells were washed three times with sterile PBS, and 100 µL of CCK-8 reagent was added to each well. After incubation at 37°C for 4 h, the absorbance at 495 nm was measured using a microplate reader.

[0057] The results are as follows Figure 12 As shown, when the concentration of PMn-Au@CTS reached 300 μg / mL, the survival rate of both cell types remained above 80%, indicating that PMn-Au@CTS has good biocompatibility.

[0058] Examples 2-5 Referring to the preparation method of Example 1, the mass ratio of PMn-Au to chitosan in step S3 was adjusted while other conditions remained unchanged, and composite materials with different ratios were prepared.

[0059] Tests showed that when the mass ratio of PMn-Au to chitosan was 1:1, 1:2, and 1:3, the resulting materials all exhibited good antibacterial properties and wound healing promotion effects.

[0060] Examples 6-8 Referring to the preparation method of Example 1, the mass ratio of PMn, chloroauric acid and sodium borohydride in step S2 was adjusted, while other conditions remained unchanged, to obtain composite materials with different ratios.

[0061] Tests showed that when the mass ratio of PMn, chloroauric acid and sodium borohydride was 10:5:5.68, 10:10:11.35, and 10:20:22.70, the resulting materials all exhibited good antibacterial properties and wound healing promotion effects.

[0062] Industrial applicability The glucose-responsive cascade antibacterial nanomaterials and their preparation method provided by this invention can be effectively applied to the preparation of drugs or medical dressings that promote the healing of diabetic wounds. This material achieves highly efficient treatment of diabetic wound infections through multiple mechanisms, including glucose-responsive cascade catalysis, photothermal synergistic bactericidal action, and charge-flipping targeted binding. The preparation method is simple, the conditions are mild, and it is easy to scale up production, possessing broad clinical application prospects and market economic value.

[0063] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A glucose-responsive cascade antibacterial nanomaterial, characterized in that: The nanomaterial has a core-shell structure, including a Mn-doped Prussian blue core, which is cubic in shape and has a particle size of 150–160 nm. Gold nanoparticles loaded on the surface of the core; and a chitosan layer wrapped around the outermost layer; The overall particle size of the antibacterial nanomaterial is 190–210 nm.

2. The glucose-responsive cascade antibacterial nanomaterial according to claim 1, characterized in that: The gold nanoparticles are chemically bonded and anchored to the surface of the Prussian blue core via in-situ reduction.

3. A method for preparing glucose-responsive cascade antibacterial nanomaterials as described in claim 1 or 2, characterized in that, Includes the following steps: S1 and PMn were synthesized using a solvothermal method, in which a manganese source solution was added dropwise to a potassium ferricyanide solution and reacted under acidic conditions at 80°C. After centrifugation, washing, and drying, PMn was obtained. The synthesis of S2 and PMn-Au involves dispersing PMn in water, adding chloroauric acid, stirring in the dark, and then adding sodium borohydride for in-situ reduction reaction, which allows gold nanoparticles to grow in situ on the surface of PMn. The reaction product is centrifuged, washed, and dried to obtain PMn-Au loaded with gold nanoparticles. The synthesis of S3 and PMn-Au@CTS involved adding a PMn-Au solution dropwise to a chitosan solution, stirring to fully encapsulate the chitosan, and then centrifuging, washing, and drying to obtain the final product PMn-Au@CTS.

4. The preparation method according to claim 3, characterized in that: In step S1, the reaction temperature of the solvothermal method is 80°C and the reaction time is 20 h.

5. The preparation method according to claim 3, characterized in that: In step S1, the concentrations of both potassium ferricyanide and manganese source are 2 mmol / L; the acidic condition is adjusted by hydrochloric acid, and the concentration of hydrochloric acid is 0.01 mol / L.

6. The preparation method according to claim 3, characterized in that: In step S2, the mass ratio of PMn, chloroauric acid and sodium borohydride is 10:5 to 10:5.68 to 11.

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7. The preparation method according to claim 3, characterized in that: In step S2, gold nanoparticles are chemically bonded and anchored to the PMn surface, resulting in a uniform and robust load.

8. The preparation method according to claim 3, characterized in that: In step S3, the mass ratio of PMn-Au to chitosan is 1:1 to 3.

9. The use of a glucose-responsive cascade antibacterial nanomaterial as described in claim 1 or 2 in the preparation of a medicament for promoting diabetic wound healing.

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