Multi-mode synergistic antibacterial and wound healing promoting material based on metal organic framework as well as preparation and application of multi-mode synergistic antibacterial and wound healing promoting material

Abstract

The invention discloses a multi-mode synergistic antibacterial and wound healing promoting material based on a metal organic framework as well as preparation and application of the multi-mode synergistic antibacterial and wound healing promoting material, and relates to the technical field of nano antibacterial materials. The method comprises the following steps: dissolving a carboxyl-containing type II photosensitizer, 1-ethyl-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide in dimethyl sulfoxide, and stirring in a dark place at room temperature to obtain a mixed solution; the metal organic framework loaded with the photosensitizer is obtained; the preparation method comprises the following steps: mixing a certain concentration of metal organic framework solution loaded with a photosensitizer with a protein solution containing iron ions, and standing to obtain the multi-mode composite material capable of synergistically resisting bacteria and promoting wound healing. According to the invention, the water-insoluble II-type photosensitizer is dispersed in the microporous structure of the metal organic framework, so that the II-type photodynamic performance is effectively improved.

Description

Technical Field

[0001] The present invention relates to the technical field of nano antibacterial materials, and in particular to a multimodal synergistic antibacterial and wound healing promoting material based on a metal organic framework, and the preparation and application thereof. Background Art

[0002] Epidemiological data as of 2024 show that bacterial infections cause approximately 7.7 million deaths worldwide each year, a dire situation that poses an unprecedented challenge to global public health systems. In clinical practice, antibiotics have long been the mainstay of combating bacterial infections. However, the widespread and inappropriate use of antibiotics has led to a series of serious problems: On the one hand, the inherent toxic side effects of antibiotics pose potential risks to patients' organ function; on the other hand, the rapid evolution of bacterial resistance has led to the emergence of multidrug-resistant strains. The World Health Organization has repeatedly warned that without effective intervention, humanity could face the threat of a "post-antibiotic era," in which common bacterial infections could once again become incurable.

[0003] In this context, photodynamic therapy (PDT), as an innovative antibacterial strategy, has shown significant advantages due to its unique mechanism of action. Compared with traditional antibiotics, PDT has the following outstanding features: (1) high spatiotemporal selectivity, enabling precise targeted therapy; (2) low systemic toxicity and manageable side effects; (3) low likelihood of inducing bacterial resistance; and (4) relatively low treatment costs. These characteristics make it a potential solution to combat drug-resistant bacterial infections.

[0004] However, current photodynamic antibacterial technology still faces several key challenges. The photosensitizers reported in the study are mainly represented by porphyrin derivatives. This type of type II photosensitizer has obvious limitations: first, its hydrophobic properties lead to poor water solubility, and molecular aggregation is prone to occur in the physiological environment, which seriously affects the photodynamic activity; second, the singlet oxygen quantum yield is limited and the antibacterial efficacy is insufficient. More importantly, it is difficult to achieve broad-spectrum and efficient killing of various pathogens by relying solely on the singlet oxygen produced by the type II photodynamic pathway, which greatly limits its application in the treatment of complex infections. These technical bottlenecks urgently need to be broken through through material innovation and mechanism research. Summary of the Invention

[0005] In view of the deficiencies in the above-mentioned background technology, the present invention mainly solves the problems of low efficiency of active oxygen generation and single antibacterial mode in existing photodynamic antibacterial technology. The present invention provides a multimodal synergistic antibacterial and wound healing material based on a metal organic framework, and its preparation and application. The present invention constructs a high-efficiency antibacterial material based on the multimodal synergistic enhancement mechanism of active oxygen, which provides an innovative solution to the problems of bacterial resistance and complex infection treatment. The preparation method provided by the present invention has a simple process and good repeatability, and the strategy based on multimodal synergistic antibacterial provides important guidance for the development of new antibacterial materials. The material provided by the present invention achieves high-efficiency antibacterial and wound healing through the synergistic effect of type I photodynamic therapy, type II photodynamic therapy and chemodynamic therapy.

[0006] This invention, based on the encapsulation of a metal-organic framework (MOF), solves the problem of hydrophobic aggregation of type II photosensitizers, significantly improving the efficiency of photodynamic therapy. It also leverages the photocatalytic properties of the MOF to achieve type I photodynamic therapy, and uses surface-modified iron-containing proteins to convert H₂O₂ into the more oxidative ·OH, enabling self-supply of H₂O₂ for chemodynamic therapy. Furthermore, through multi-component collaborative assembly, a nanocomposite with broad-spectrum antimicrobial properties was constructed, demonstrating excellent antimicrobial efficacy and wound healing in both in vitro and in vivo experiments.

[0007] The first object of the present invention is to provide a method for preparing a multimodal synergistic antibacterial and wound healing promoting material based on a metal organic framework, which comprises the following steps:

[0008] Dissolve a carboxyl-containing type II photosensitizer, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide in dimethyl sulfoxide, and stir in the dark at room temperature to obtain a mixed solution;

[0009] The metal source and the organic ligand solution are added to the mixed solution respectively, and reacted under stirring conditions to obtain a metal organic framework loaded with a photosensitizer;

[0010] A photosensitizer-loaded metal-organic framework solution of a certain concentration is mixed with a protein solution containing iron ions, and after static treatment, a multimodal synergistic antibacterial and wound-healing composite material is obtained.

[0011] Preferably, the ratio of the carboxyl-containing type II photosensitizer to dimethyl sulfoxide is 1 mg: 150-250 μL;

[0012] The mass ratio of the carboxyl-containing type II photosensitizer to N-hydroxysuccinimide is 1:1-3;

[0013] The mass ratio of N-hydroxysuccinimide to 1-ethyl-(3-dimethylaminopropyl)carbodiimide is 1:1-2.

[0014] Preferably, the mass ratio of the carboxyl-containing type II photosensitizer to the metal source is 1:500-1000; and the mass ratio of the organic ligand in the organic ligand solution to the metal source is 1:10-15.

[0015] Preferably, the mass concentration ratio of the protein containing iron ions to the metal organic framework loaded with photosensitizer is 1:1-5.

[0016] Preferably, the carboxyl-containing type II photosensitizer is one or more of protoporphyrin IX, benzochlorin, pyropheophorbide-a, and dihydrochlorin e6; the metal source is Zn(NO3)2·6H2O; and the organic ligand solution is a methanol solution containing 2-methylimidazole (2-MIM).

[0017] Preferably, the protein containing iron ions is one of cytochrome, hemoglobin, myoglobin, iron-molybdenum protein and iron-sulfur protein.

[0018] Preferably, the stirring time at room temperature in the dark is 20 min to 60 min.

[0019] Preferably, the concentration of the metal organic framework solution loaded with photosensitizer is 1-3 mg mL -1

[0020] The second object of the present invention is to provide a multimodal synergistic antibacterial and wound healing promoting material based on metal organic framework.

[0021] The third object of the present invention is to provide a use of the above-mentioned material in the preparation of multimodal synergistic antibacterial and wound healing promoting drugs.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The present invention provides a multimodal synergistic antibacterial and wound healing-promoting material based on a metal-organic framework, as well as its preparation and application. The present invention first dissolves a carboxyl-containing Type II photosensitizer, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide in a small amount of solvent and stirs in the dark at room temperature. A metal source and an organic ligand solution are then added to the solution, reacted under certain conditions to obtain a precipitate, which is then centrifuged and washed before being dispersed in a solvent for later use. Finally, the solution at a certain concentration is mixed with a protein solution containing iron ions and allowed to stand for a final product. The present invention disperses the water-insoluble Type II photosensitizer in the microporous structure of the metal-organic framework, effectively improving Type II photodynamic performance. The metal-organic framework constructed in the present invention can achieve Type I photodynamic properties. The iron-containing protein modified on the surface of the metal-organic framework can achieve chemodynamic activity through the Fenton reaction. Therefore, the nanocomposite material prepared by the present invention exhibits a multimodal form with synergistic Type I and Type II photodynamics and chemodynamics, ultimately achieving efficient antibacterial and wound healing.

[0024] The present invention generates a variety of ROS ( 1 O2, O2 - , H2O2, and ·OH), destroying bacterial structure and inhibiting drug resistance, resulting in antibacterial effects. Furthermore, while maintaining high bactericidal efficacy, the material modulates inflammatory responses, promotes collagen deposition, and epidermal regeneration, while its high biocompatibility ensures safety. ZIF-8 encapsulation and Cyt c modification enable the spatiotemporally controlled release of ROS, overcoming the limitations of traditional photosensitizer aggregation and single-treatment modalities, and providing a new strategy for the treatment of infected wounds.

[0025] Based on the metal-organic framework nanocomposite material, the present invention significantly improves the efficiency of reactive oxygen generation by integrating three treatment modes: type I photodynamic therapy, type II photodynamic therapy, and chemodynamic therapy, and can achieve a highly efficient broad-spectrum antibacterial effect.

[0026] This study constructs a high-performance antimicrobial material at the nanoscale based on a multimodal reactive oxygen species synergistic enhancement mechanism. This composite material is then loaded into medical dressings to facilitate its application in wound treatment. This innovative strategy, based on metal-organic frameworks (MOFs), demonstrates multimodal synergistic antimicrobial activity and provides a novel solution for the clinical treatment of drug-resistant bacterial infections and wound repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Schematic diagram of the structure of the multimodal synergistic antibacterial composite material based on metal-organic architecture in Example 1.

[0028] Figure 2These are optical photographs of ZIF-8, Ce6@ZIF-8 and Ce6@ZIF-8@Cyt c synthesized in Example 1 under different conditions.

[0029] Figure 3 UV-vis absorption spectra and fluorescence emission spectra of Ce6, Ce6@ZIF-8 and Ce6@ZIF-8@Cyt c.

[0030] Figure 4 This is the morphological characterization of the multimodal synergistic antibacterial composite material based on metal-organic framework in Example 1.

[0031] Figure 5 This is the particle size distribution diagram of Ce6@ZIF-8 and Ce6@ZIF-8@Cyt c in aqueous solution in Example 1.

[0032] Figure 6 These are the test results of the ROS production ability of different samples in Example 1 using the DCFH probe under light-shielding or light-irradiation conditions.

[0033] Figure 7 Optical photographs of Escherichia coli and Staphylococcus aureus colonies treated with physiological saline, ZIF-8, Ce6@ZIF-8, and Ce6@ZIF-8@Cyt c in Example 1 under light-protected or light-exposed conditions; statistical results of the antibacterial activity against Escherichia coli and Staphylococcus aureus obtained based on the spread plate method.

[0034] Figure 8 The activity of different concentrations of Ce6@ZIF-8@Cyt c after co-incubation with L929 cells and the hemolysis of mouse red blood cells in Example 1 are shown.

[0035] Figure 9 These are photos of the wounds of mice infected with Staphylococcus aureus treated with physiological saline, ZIF-8, Ce6@ZIF-8, and Ce6@ZIF-8@Cyt c in Example 1 on days 0, 3, 7, and 12. DETAILED DESCRIPTION

[0036] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention is further described below with reference to specific embodiments and drawings, but the embodiments are not intended to limit the present invention.

[0037] The purpose of the present invention is to provide a multimodal synergistic antibacterial and wound healing promoting material based on a metal organic framework, and a preparation method and application thereof.

[0038] To achieve multimodal synergy to enhance antibacterial and wound healing effects, the present invention constructs a metal-organic framework composite material loaded with photosensitizers modified with iron ions to achieve multimodal antibacterial synergy between type I and II photodynamic therapy and chemodynamic therapy. The type II photosensitizer is isolated by the metal-organic framework, improving the efficiency of type II photodynamic therapy while simultaneously achieving type I photodynamic therapy. The iron-containing protein can achieve chemodynamic therapy. Multimodal synergy is achieved to enhance antibacterial and wound healing effects. By integrating the three treatment modes of type I photodynamic therapy, type II photodynamic therapy, and chemodynamic therapy, the efficiency of reactive oxygen species generation is significantly improved, achieving efficient broad-spectrum antibacterial effects, and constructing a high-performance antibacterial material based on a multimodal reactive oxygen species synergistic enhancement mechanism. The composite material is further loaded into a medical dressing to promote its application in wound treatment. This achieves an innovative strategy for multimodal synergistic antibacterial synergy based on metal-organic frameworks, providing a new solution for the clinical treatment of drug-resistant bacterial infections and wound repair. The composite material developed in the present invention has a precise nanostructure, excellent biocompatibility and unique multimodal synergistic production characteristics. It is an ideal nanomaterial for achieving efficient antibacterial treatment by synergistically enhancing the effects of type I photodynamic therapy, type II photodynamic therapy and chemodynamic therapy.

[0039] In order to achieve the above objectives, the first aspect of the present invention provides a method for preparing a multimodal synergistic antibacterial and wound healing promoting material based on a metal organic framework. Figure 1 As shown, the following steps are included:

[0040] A carboxyl-containing type II photosensitizer, 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC), and N-hydroxysuccinimide (NHS) were dissolved in dimethyl sulfoxide (DMSO) and stirred in the dark at room temperature to obtain a mixed solution;

[0041] The metal source and organic ligand solution were added to the mixed solution respectively, and reacted for 20 minutes under stirring to obtain a metal-organic framework loaded with a photosensitizer;

[0042] 1~3mg mL -1 The metal-organic framework solution loaded with photosensitizer is mixed with the protein solution containing iron ions, and after static treatment, a multimodal synergistic antibacterial and wound healing composite material is obtained.

[0043] The present invention assembles a hydrophobic photosensitizer and a hydrophilic metal-organic framework into a nanocomposite through the coordination encapsulation effect of the metal-organic framework, and then modifies the protein containing iron ions in the functional component, thereby constructing a high-performance antibacterial material based on the multimodal synergistic mechanism of type I photodynamic therapy, type II photodynamic therapy and chemodynamic therapy.

[0044] The formation of the photosensitizer-loaded metal-organic framework complex in the present invention is mainly driven by the coordination self-assembly of the metal source and the organic ligand, and the photosensitizer molecules are encapsulated in the metal-organic framework pores through hydrophobic interaction; the protein containing iron ions electrostatically interacts with the photosensitizer-loaded metal-organic framework and is evenly distributed on the surface of the complex to form a stable structure.

[0045] The ratio of carboxyl-containing type II photosensitizer to dimethyl sulfoxide is 1 mg: 150-250 μL;

[0046] The mass ratio of the carboxyl-containing type II photosensitizer to N-hydroxysuccinimide is 1:1-3;

[0047] The mass ratio of N-hydroxysuccinimide to 1-ethyl-(3-dimethylaminopropyl)carbodiimide is 1:1-2.

[0048] The mass ratio of the carboxyl-containing type II photosensitizer to the metal source is 1:500-1000; the mass ratio of the organic ligand in the organic ligand solution to the metal source is 1:10-15.

[0049] The mass concentration ratio of the protein containing iron ions to the metal organic framework loaded with photosensitizer is 1:1-5.

[0050] The carboxyl-containing type II photosensitizer is one or more of protoporphyrin IX, benzochlorin, pyropheophorbide-a, and dihydrochlorin e6; it has strong photosensitivity and can generate singlet oxygen under light conditions to achieve type II photodynamic therapy.

[0051] The metal source is Zn(NO3)2·6H2O; the organic ligand solution is a methanol solution of 2-methylimidazole (2-MIM).

[0052] The protein containing iron ions is one of cytochrome, hemoglobin, myoglobin, iron-molybdenum protein and iron-sulfur protein; it has peroxidase-like activity and can convert H2O2 into ·OH to achieve chemokinetic therapeutic effects.

[0053] The stirring time at room temperature in the dark is 20 min to 60 min.

[0054] The protein containing iron ions and the metal organic framework loaded with photosensitizer have a mass concentration ratio of 1:1 to 5, and the modification is carried out under aqueous solution conditions, and the reaction is carried out at room temperature for 30 minutes under static conditions; wherein the concentration of the metal organic framework solution loaded with photosensitizer is

[0055] The metal organic framework loaded with a photosensitizer prepared in the present invention is one of MOF-5, HKUST-1, ZIF-8, UiO-66, and MIL-101, and has an adjustable pore structure, excellent biocompatibility, and the ability to efficiently encapsulate organic molecules.

[0056] The second aspect of the present invention provides a multimodal synergistic antibacterial and wound healing promoting material based on a metal organic framework.

[0057] The third aspect of the present invention provides a use of the above-mentioned material in the preparation of multimodal synergistic antibacterial and wound healing promoting drugs.

[0058] During the application process, the multimodal antibacterial composite material is attached to the non-woven fabric substrate by soaking using a medical dressing carrier to form an antibacterial dressing.

[0059] Wound types include bacterially infected wounds, burn wounds, and postoperative incisions. For infected wounds, the material can simultaneously exert dual functions of antibacterial and promoting healing.

[0060] The antibacterial mechanism is a multimodal synergistic mechanism combining Type I photodynamic therapy, Type II photodynamic therapy, and chemodynamic therapy. The metal-organic framework photocatalytically generates reactive oxygen species (ROS) that achieve Type I PDT, the photosensitizer generates singlet oxygen that achieves Type II PDT, and the cytochrome converts H₂O₂ into ·OH via the Fenton reaction, achieving chemodynamic therapy. These three mechanisms work synergistically to significantly enhance ROS production, resulting in highly effective bacterial killing.

[0061] It should be noted that the experimental methods used in the present invention are all conventional methods unless otherwise specified; the reagents and materials used are all commercially available unless otherwise specified.

[0062] Example 1

[0063] A method for preparing a multimodal synergistically enhanced photodynamic antibacterial and wound healing-promoting material based on a metal-organic framework comprises the following steps:

[0064] 1) First, chlorin e6 (0.5 mg), NHS (0.8 mg), and EDC (1.2 mg) were dissolved in 100 μL of DMSO and stirred at room temperature in the dark for 30 minutes to obtain a dark green solution. This solution was then transferred to 6 mL of methanol to obtain a mixed solution. 294 mg of Zn(NO₃)₂·6H₂O was then added to the mixed solution and sonicated for several minutes to obtain a transparent off-white solution. Finally, 24 mL of methanol containing 2-MIM (625 mg) was added dropwise. After stirring for 20 minutes, the resulting product was centrifuged at 10,000 rpm for 5 minutes, washed with methanol and deionized water, and dispersed in 1 mL of water to obtain a Ce6@ZIF-8 aqueous solution.

[0065] 2) 2mg mL -1 Ce6@ZIF-8 aqueous solution with 1 mg mL -1 The mixture was mixed with the Cyt c aqueous solution, allowed to stand for 30 minutes and then centrifuged for washing to obtain the product Ce6@ZIF-8@Cyt c.

[0066] Example 2

[0067] Same as Example 1, except that

[0068] Ce6 (0.5 mg), NHS (0.5 mg) and EDC (1.2 mg) were dissolved in 100 μL of DMSO solution.

[0069] Example 3

[0070] Same as Example 1, except that

[0071] Ce6 (0.5 mg), NHS (1.0 mg) and EDC (1.2 mg) were dissolved in 100 μL of DMSO solution.

[0072] Example 4

[0073] Same as Example 1, except that

[0074] Ce6 (0.5 mg), NHS (1.5 mg) and EDC (1.2 mg) were dissolved in 100 μL of DMSO solution.

[0075] Example 5

[0076] Same as Example 1, except that

[0077] Ce6 (0.5 mg), NHS (0.8 mg) and EDC (0.8 mg) were dissolved in 100 μL of DMSO solution.

[0078] Example 6

[0079] Same as Example 1, except that

[0080] Ce6 (0.5 mg), NHS (0.8 mg) and EDC (1.6 mg) were dissolved in 100 μL of DMSO solution.

[0081] Example 7

[0082] Same as Example 1, except that

[0083] 1 mg mL -1 Ce6@ZIF-8 aqueous solution with 1 mg mL -1 The mixture was mixed with cytochrome c aqueous solution, allowed to stand for 30 minutes and then centrifuged for washing.

[0084] Example 8

[0085] Same as Example 1, except that

[0086] 3mg mL -1 Ce6@ZIF-8 aqueous solution with 1 mg mL -1 The mixture was mixed with cytochrome c aqueous solution, allowed to stand for 30 minutes and then centrifuged for washing.

[0087] Example 9

[0088] Same as Example 1, except that

[0089] 4 mg mL -1 Ce6@ZIF-8 aqueous solution with 1 mg mL -1 The mixture was mixed with cytochrome c aqueous solution, allowed to stand for 30 minutes and then centrifuged for washing.

[0090] Example 10

[0091] Same as Example 1, except that

[0092] 5mg mL -1 Ce6@ZIF-8 aqueous solution with 1 mg mL -1 The mixture was mixed with cytochrome c aqueous solution, allowed to stand for 30 minutes and then centrifuged for washing.

[0093] In order to illustrate the relevant properties of a multimodal synergistic antibacterial composite material based on a metal organic framework provided by the present invention, it is described in conjunction with the accompanying drawings.

[0094] Figure 2 These are optical photographs of ZIF-8, Ce6@ZIF-8 and Ce6@ZIF-8@Cyt c synthesized in Example 1 under different conditions.

[0095] Figure 2 Figure a was observed under fluorescent light. The colors of the three solutions are all grayish white, with no obvious difference.

[0096] Figure 2 Figures b and c show optical photographs of the synthesized ZIF-8, Ce6@ZIF-8, and Ce6@ZIF-8@Cyt c, respectively, under blue-violet light. Exposure to 365nm blue-violet light revealed that the solutions and solids of Ce6@ZIF-8 and Ce6@ZIF-8@Cyt c exhibited red fluorescence, while the ZIF-8 solution and solid exhibited almost no fluorescence. This indicates that chlorin e6 forms a Ce6@ZIF-8 complex with ZIF-8 and that encapsulating cytochrome c has no effect on the fluorescence properties of Ce6@ZIF-8.

[0097] Figure 3 (a) UV-vis absorption spectra and (b) fluorescence emission spectra of Ce6, Ce6@ZIF-8 and Ce6@ZIF-8@Cyt c in Example 1. Figure 3 As can be seen, Ce6@ZIF-8 and Ce6@ZIF-8@Cytc both exhibit a characteristic absorption peak for chlorin e6 at 420 nm, consistent with the UV-vis absorption spectrum of chlorin e6, indicating successful encapsulation of chlorin e6. Since all three materials exhibit the strongest absorption peak at 420 nm, light of this wavelength was used to excite them and generate the corresponding fluorescence emission spectra. All three materials exhibit fluorescence emission peaks at 650 nm and 720 nm, characteristic of chlorin e6. Consequently, the composite exhibits red fluorescence under violet light, further confirming the successful loading of chlorin e6 while maintaining its optical properties.

[0098] Figure 4 This is the morphological characterization of the multimodal synergistic antibacterial composite material based on metal-organic framework in Example 1. Figure 4 It can be seen that Ce6@ZIF-8 (a) and Ce6@ZIF-8@Cyt c (b) are nanoparticles with uniform particle size, and the coating of cytochrome c has no obvious effect on the morphology of the composite material.

[0099] Figure 5 Figure 1 shows the particle size distribution of Ce6@ZIF-8 and Ce6@ZIF-8@Cyt c in aqueous solution in Example 1. 1-3 represents 3 repetitions.

[0100] Figure 5The hydrated diameter of Ce6@ZIF-8 increases with the number of tests, indicating that Ce6@ZIF-8 is unstable in solution. As the number of tests increases, the nanoparticles gradually aggregate and their particle size increases. Notably, the hydrated diameter of Ce6@ZIF-8@Cyt c remains stable at approximately 120 nm after multiple tests, further confirming that cytochrome c encapsulation effectively enhances the colloidal stability and dispersibility of Ce6@ZIF-8.

[0101] Figure 6 These are the test results of the reactive oxygen species generation ability of different samples containing Ce6, ZIF-8, Ce6@ZIF-8 and Ce6@ZIF-8@Cytc under light-shielding and light-irradiating conditions in Example 1 using 2',7'-dichlorodihydrofluorescein probe.

[0102] Figure 6 Under illumination (XL), the fluorescence intensity of 2',7'-dichlorodihydrofluorescein solutions containing ZIF-8, Ce6@ZIF-8, and Ce6@ZIF-8@Cyt c gradually increased, indicating a gradual increase in the amount of reactive oxygen species generated. This suggests that ZIF-8, Ce6@ZIF-8, and Ce6@ZIF-8@Cyt c possess the ability to generate reactive oxygen species (ROS) through light triggering. Compared to chlorin e6 and ZIF-8 alone, the fluorescence intensity of 2',7'-dichlorodihydrofluorescein solutions containing Ce6@ZIF-8 increased more rapidly, far exceeding the combined ROS generation efficiency of chlorin e6 and ZIF-8. After 4 minutes of illumination, the ROS generation efficiency of Ce6@ZIF-8 was 14 times that of ZIF-8 and 64 times that of chlorin e6. This result demonstrates that the complex of chlorin e6 and ZIF-8 can significantly enhance the generation of reactive oxygen species.

[0103] Figure 7 Optical photographs of Escherichia coli (a) and Staphylococcus aureus (c) colonies treated with physiological saline, ZIF-8, Ce6@ZIF-8, and Ce6@ZIF-8@Cyt c in Example 1 under light-protection or light conditions; statistical results of the antibacterial activity of Escherichia coli (b) and Staphylococcus aureus (d) obtained based on the spread plate method.

[0104] Figure 7 As shown, after light treatment, the samples containing the materials all exhibited significant antibacterial properties: ZIF-8, Ce6@ZIF-8, and Ce6@ZIF-8@Cyt c achieved inhibition rates of 55%, 83%, and 99%, respectively. The order of antibacterial performance among the three materials was Ce6@ZIF-8@Cyt c > Ce6@ZIF-8 > ZIF-8, which was proportional to the efficiency of reactive oxygen species production. Ce6@ZIF-8@Cyt c exhibited a broad-spectrum photodynamic therapy antibacterial effect.

[0105] Figure 8 The activity of different concentrations of Ce6@ZIF-8@Cyt c after co-incubation with L929 cells in Example 1 (a) and the hemolysis of mouse red blood cells (b).

[0106] Figure 8 It can be seen that when the concentration of Ce6@ZIF-8@Cyt c material incubated with L929 cells reached 150 μg mL -1 When the concentration of Ce6@ZIF-8@Cyt c material co-incubated with red blood cells reached 150 μg mL -1 When the hemolysis rate of red blood cells was less than 5%, it showed that Ce6@ZIF-8@Cyt c had good blood compatibility. In summary, the prepared Ce6@ZIF-8@Cyt c nanocomposite showed good biocompatibility.

[0107] Figure 9 The following are photos of wounds of mice infected with Staphylococcus aureus treated with physiological saline, ZIF-8, Ce6@ZIF-8, and Ce6@ZIF-8@Cyt c in Example 1 on days 0, 3, 7, and 12. The treatment order is (1) Saline + Dark; (2) ZIF-8 + Dark; (3) Ce6@ZIF-8 + Dark; (4) Ce6@ZIF-8@Cyt c + Dark; (5) Saline + Light; (6) ZIF-8 + Light; (7) Ce6@ZIF-8 + Light; (8) Ce6@ZIF-8@Cyt c + Light.

[0108] Figure 9 The experimental groups (ZIF-8+Light, Ce6@ZIF-8+Light, and Ce6@ZIF-8@Cyt c+Light) all healed faster than the controls (Saline+Dark, ZIF-8+Dark, Ce6@ZIF-8+Dark, Ce6@ZIF-8@Cyt c+Dark, and Saline+Light). The Ce6@ZIF-8@Cyt c+Light group had the smallest wounds and the fastest healing rate. These results suggest that the Ce6@ZIF-8@Cyt c composite material can promote rapid wound healing under light conditions.

[0109] It should be noted that, in the accompanying drawings, XL represents light conditions, and Dark represents dark conditions.

[0110] In summary, the present invention provides a metal-organic framework-based multimodal synergistically enhanced photodynamic antibacterial and wound healing material, as well as its preparation method and application. Through the coordination and encapsulation effect of the metal-organic framework, the present invention assembles the hydrophobic photosensitizer dihydrochlorin e6 with the hydrophilic ZIF-8 carrier to form a nanocomposite, and then modifies the functional component cytochrome c to construct a highly effective antibacterial material based on a multimodal synergistic mechanism of type I photodynamic therapy, type II photodynamic therapy, and chemodynamic therapy. The resulting Ce6@ZIF-8@Cyt c nanocomposite solves the problem of the photosensitizer dihydrochlorin e6's easy aggregation in an aqueous environment and significantly improves the efficiency of type II photodynamic therapy. The ZIF-8 carrier produces ·O2- and H2O2 through photocatalysis to achieve type I photodynamic therapy, while cytochrome c converts H2O2 into ·OH through the Fenton reaction to achieve chemodynamic therapy. The composite material is further loaded into medical dressings for wound treatment, showing excellent therapeutic effects in inhibiting bacterial infection and promoting wound healing. The preparation method provided by the present invention has a simple process and good repeatability. At the same time, the strategy based on the synergistic enhancement of multimodal active oxygen provides an innovative solution for the development of new antibacterial materials and the treatment of drug-resistant bacterial infections.

[0111] The present invention describes preferred embodiments and their effects. However, those skilled in the art, once informed of the basic inventive concept, may make additional changes and modifications to these embodiments. Therefore, it is intended that the appended claims be interpreted to include the preferred embodiments as well as all changes and modifications that fall within the scope of the invention.

[0112] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a multimodal synergistic antibacterial and wound healing-promoting material based on a metal-organic framework, characterized in that: The following steps are involved: Dissolve a carboxyl-containing type II photosensitizer, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide in dimethyl sulfoxide, and stir in the dark at room temperature to obtain a mixed solution; The metal source and the organic ligand solution are added to the mixed solution respectively, and reacted under stirring conditions to obtain a metal organic framework loaded with a photosensitizer; A photosensitizer-loaded metal-organic framework solution of a certain concentration is mixed with a protein solution containing iron ions, and after static treatment, a multimodal synergistic antibacterial and wound-healing composite material is obtained.

2. The method for preparing a metal organic framework-based multimodal synergistic antibacterial and wound healing promoting material according to claim 1, characterized in that: The ratio of the carboxyl-containing type II photosensitizer to dimethyl sulfoxide is 1 mg: 150-250 μL; the mass ratio of the carboxyl-containing type II photosensitizer to N-hydroxysuccinimide is 1:1-3; and the mass ratio of N-hydroxysuccinimide to 1-ethyl-(3-dimethylaminopropyl)carbodiimide is 1:1-2.

3. The method for preparing a metal organic framework-based multimodal synergistic antibacterial and wound healing promoting material according to claim 1, characterized in that: The mass ratio of the carboxyl-containing type II photosensitizer to the metal source is 1:500-1000; the mass ratio of the organic ligand in the organic ligand solution to the metal source is 1:10-15.

4. The method for preparing a metal organic framework-based multimodal synergistic antibacterial and wound healing promoting material according to claim 1, characterized in that: The mass concentration ratio of the protein containing iron ions to the metal organic framework loaded with photosensitizer is 1:1-5.

5. The method for preparing a metal organic framework-based multimodal synergistic antibacterial and wound healing promoting material according to claim 1, characterized in that: The carboxyl-containing type II photosensitizer is one or more of protoporphyrin IX, benzochlorin, pyropheophorbide-a, and chlorin e6; the metal source is Zn(NO3)2·6H2O; and the organic ligand solution is a methanol solution containing 2-methylimidazole (2-MIM).

6. The method for preparing a metal organic framework-based multimodal synergistic antibacterial and wound healing promoting material according to claim 1, characterized in that: Proteins containing iron ions are one of cytochrome, hemoglobin, myoglobin, iron-molybdenum protein and iron-sulfur protein.

7. The method for preparing a metal organic framework-based multimodal synergistic antibacterial and wound healing promoting material according to claim 1, characterized in that: The stirring time at room temperature in the dark is 20 min to 60 min.

8. The method for preparing a metal organic framework-based multimodal synergistic antibacterial and wound healing promoting material according to claim 1, characterized in that: The concentration of the metal organic framework solution loaded with photosensitizer is 1-3 mg mL -1 .

9. A metal-organic framework-based multimodal synergistic antibacterial and wound healing promoting material prepared by the method according to any one of claims 1 to 8.

10. Use of the material according to claim 9 in preparing multimodal synergistic antibacterial and wound healing promoting drugs.

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