Use of an iron-based composite material in the treatment of diabetic wounds

Abstract

The application discloses application of an iron-based composite material in treatment of a diabetic wound, and has the advantages of simple preparation process, green economy, low cost and mass production, etc. The iron-based composite material has the functions of antibiosis, antioxidation stress resistance and proangiogenesis through a core-shell structure design, and has a remarkable effect in treatment of the diabetic wound.

Description

Technical Field

[0001] This invention belongs to the field of iron-based composite materials, specifically relating to the application of an iron-based composite material in the treatment of diabetic wounds. Background Technology

[0002] Diabetes is a chronic disease affecting hundreds of millions of people worldwide, profoundly impacting human health. Besides persistent high blood sugar, it is often accompanied by various complications, among which diabetic chronic wounds are particularly problematic due to their difficulty in healing. Because of the persistent inflammatory response and hypoxic microenvironment at the wound site, tissue repair struggles to smoothly transition from the inflammatory phase to the proliferative phase, leading to a slow healing process and a high susceptibility to secondary bacterial infections. Therefore, promoting the healing of diabetic chronic wounds has become an important research direction in the field of medical rehabilitation.

[0003] Nanozymes are a class of artificial enzymes that combine the properties of nanomaterials with enzyme-like catalytic functions, and have shown broad application prospects in the treatment of diabetic wounds in recent years. In terms of research findings, nanozymes, with their excellent catalytic activity, good stability, and tunable physicochemical properties, can exert multiple therapeutic effects targeting the complex pathological microenvironment of diabetic wounds. For example, nanozymes with superoxide dismutase (SOD)-like activity can efficiently remove excessively accumulated reactive oxygen species in wounds, alleviate oxidative stress, and reduce persistent inflammatory responses; some nanozymes can catalyze the decomposition of hydrogen peroxide accumulated in hypoxic microenvironments through catalase (CAT)-like activity to produce oxygen, improving local hypoxia and thus promoting angiogenesis and tissue repair. Through rational design, nanozymes can also be combined with other functional materials to construct responsive drug delivery systems or multifunctional hydrogel dressings, achieving multidimensional regulation of the wound microenvironment and significantly accelerating the wound healing process. However, nanozymes often possess multiple enzyme activities, such as oxidase (OXD) and peroxidase (POD) activities. Although OXD and POD activities have antibacterial capabilities, they can also increase oxidative stress on wounds. Therefore, it is essential to rationally design nanozymes and develop a composite material with targeted application of enzyme activity and function. Summary of the Invention

[0004] Purpose of the invention: The technical problem to be solved by the present invention is to provide an application of iron-based composite material in the treatment of diabetic wounds, which has antibacterial, antioxidant stress and angiogenesis-promoting capabilities.

[0005] Technical Solution: To solve the above-mentioned technical problems, this invention provides an application of an iron-based composite material in the preparation of drugs or reagents for improving and / or treating diabetic wounds. The iron-based composite material is PCN-Fe@Cu, wherein PCN-Fe@Cu is Cu co-loaded on a core-shell structure PCN-Fe@TA. 2+ It is found that the core-shell structure PCN-Fe@TA is obtained by adding tannic acid to the iron-based metal-organic framework nanoenzyme PCN-Fe for shell modification.

[0006] The diabetic wounds mentioned above include diabetic infected wounds.

[0007] The preparation method of the iron-based composite material includes the following steps:

[0008] (1) Iron porphyrin, zirconium oxychloride octahydrate and benzoic acid were dissolved in N,N-dimethylformamide, heated and stirred until homogeneous; the mixture was placed in an oil bath and stirred slowly. After the reaction was completed, the mixture was cooled to room temperature and washed with DMF by centrifugation to obtain iron-based metal-organic framework nanozyme PCN-Fe.

[0009] (2) The supernatant of the nanozyme PCN-Fe was removed by centrifugation, and deionized water was added to disperse it to obtain an aqueous solution of PCN-Fe nanozyme; the aqueous solution of PCN-Fe nanozyme was stirred with a magnetic stirrer, and after being stirred evenly, TA was added and stirred again. The precipitate was collected by centrifugation and washed with deionized water to obtain the core-shell structure PCN-Fe@TA;

[0010] (3) PCN-Fe@TA was dispersed in deionized water and stirred with a magnetic stirrer. After it was fully dispersed, copper dichloride was added and stirred until the solution turned dark brown. The precipitate was collected by centrifugation and washed with deionized water to obtain the iron-based composite material PCN-Fe@Cu.

[0011] In step (1), the mass ratio of iron porphyrin, zirconium oxychloride octahydrate and benzoic acid is 1:3:30~1:3:50.

[0012] In step (1), the oil bath temperature is 90℃ and the reaction time is 5h.

[0013] In step (2), the mass ratio of PCN-Fe to tannic acid is 2:1 to 5:1.

[0014] In step (2), the concentration of PCN-Fe is 5~40 μg / mL.

[0015] In step (3), the mass ratio of PCN-Fe@TA to CuCl2 is 2:1 to 5:1.

[0016] The concentration of PCN-Fe@TA in step (3) is 5~40 μg / mL.

[0017] The iron-based composite material is used to prepare antibacterial, antioxidant, and / or angiogenic drugs or preparations.

[0018] The iron-based composite material described in this invention is prepared by modifying the surface of an iron-containing nanoenzyme and forming a core-shell structure through self-assembly. This refers to loading other functional elements into the shell of the iron-based nanomaterial to prepare an iron-based composite material.

[0019] This composite material possesses antibacterial, antioxidant, and angiogenesis-promoting capabilities. The antibacterial capability refers to the antibacterial components in the iron-based composite shell, which can be used for antibacterial treatment of diabetic wounds. The antioxidant stress capability refers to the antioxidant stress resistance of the iron-based nanoenzymes in the iron-based composite core. The angiogenesis-promoting capability refers to the angiogenesis-promoting ability of other functional elements co-loaded in the iron-based composite shell. The diabetic wound treatment refers to an integrated treatment approach based on the multi-component composition of the iron-based composite material, achieving antibacterial, antioxidant, and angiogenesis-promoting effects on diabetic wounds, thus promoting wound healing.

[0020] Furthermore, the iron-based nanozyme core includes, but is not limited to, iron-containing metal-organic framework nanozymes, iron oxide nanozymes, and single-atom iron-based nanozymes; the shell modifiers include, but are not limited to, polymeric compounds, small-molecule polymers, and natural organic molecular compounds; the self-assembly methods include, but are not limited to, electrostatic adsorption, covalent self-assembly, and non-covalent self-assembly; and the shell co-supporting elements include, but are not limited to, biomedical drug molecules, metal ions, or other types of compounds.

[0021] The present invention also describes a method for preparing iron-based composite materials, which specifically includes the following steps:

[0022] (1) Iron porphyrin, zirconium oxychloride octahydrate and benzoic acid were dissolved in N,N-dimethylformamide (DMF), heated and stirred evenly; placed in an oil bath at 90 ℃ and stirred slowly for 5 h. After the reaction was completed, the mixture was cooled to room temperature and washed three times by centrifugation with DMF to obtain iron-based metal-organic framework nanozyme PCN-Fe.

[0023] (2) The iron-based metal-organic framework nanozyme PCN-Fe in step (1) was modified with a shell. The PCN-Fe nanozyme was centrifuged to remove the supernatant, and then deionized water was added to disperse it to obtain an aqueous solution of PCN-Fe nanozyme. The PCN-Fe nanozyme aqueous solution was stirred with a magnetic stirrer. After stirring evenly, TA was added and stirring was continued for 30 minutes. The precipitate was collected by centrifugation and washed three times with deionized water to obtain the core-shell structure PCN-Fe@TA.

[0024] (3) The core-shell structure PCN-Fe@TA co-loaded with Cu obtained in step (2) 2+ PCN-Fe@TA was dispersed in deionized water and stirred with a magnetic stirrer. After full dispersion, copper dichloride (CuCl2) was added and stirring was continued for more than 30 minutes until the solution turned dark brown. The precipitate was collected by centrifugation and washed three times with deionized water to obtain an iron-based composite material PCN-Fe@Cu.

[0025] When the iron-based composite material is PCN-Fe@Cu, the concentration is 5~40 μg / mL.

[0026] Preferably, the concentration of the iron-based composite material used is 5~30 μg / mL.

[0027] More preferably, the concentration of the iron-based composite material used is 5~20 μg / mL.

[0028] More preferably, the concentration of the iron-based composite material used is 5~10 μg / mL.

[0029] The principle of this invention: The PCN-Fe@Cu prepared in this invention organically integrates the broad-spectrum antibacterial activity of tannic acid, the SOD / CAT-like enzyme-catalyzed antioxidant capacity of the PCN-Fe core, and the angiogenesis-promoting function of the Cu²⁺ shell. Tannic acid first provides sustained antibacterial protection, inhibiting wound infection; simultaneously, PCN-Fe enzyme mimics efficiently scavenging excess reactive oxygen species locally, alleviating oxidative stress, and creating a low-inflammatory microenvironment for tissue repair; furthermore, Cu²⁺ further exerts its angiogenesis-promoting effect, accelerating angiogenesis and improving nutrient and oxygen supply. These three components work synergistically to overcome the healing barriers of diabetic and infected wounds simultaneously through multiple stages—anti-infection, anti-oxidation, and angiogenesis—achieving rapid and high-quality wound repair.

[0030] Beneficial Effects: Compared with existing technologies, this invention has the following significant advantages: Through a core-shell structure design, it integrates three functions: antibacterial, anti-oxidative stress, and pro-angiogenesis. The natural compounds in the shell provide antibacterial properties, while the iron-based MOF nanozyme in the core (PCN-Fe) scavenges reactive oxygen species and alleviates oxidative stress through SOD-like and CAT-like activities. The pro-angiogenic molecules in the shell effectively promote angiogenesis, thus achieving comprehensive treatment of diabetic wounds. Addressing the issue that existing nanozymes may exacerbate oxidative stress due to their multiple enzyme activities, this invention retains beneficial enzyme activities (SOD-like and CAT-like) while introducing antibacterial and pro-angiogenic functions, achieving targeted application of enzyme activity and therapeutic function. The composite material, used in the treatment of diabetic wounds as an application example, validates its therapeutic potential in complex pathological microenvironments. Furthermore, by replacing the type of iron-based nanozyme in the core, shell modifications, or other self-assembling components, this preparation strategy can be extended to therapeutic research for various other diseases, demonstrating strong versatility and scalability. This invention provides a novel composite material with multiple functions for the treatment of diabetic wounds, and expands the application ideas of iron-based nanozymes in the field of tissue repair and regenerative medicine. Attached Figure Description

[0031] Figure 1 This is a schematic diagram illustrating the preparation of the iron-based composite material according to the present invention;

[0032] Figure 2 Transmission electron microscope images of iron-based nanozymes and iron-based composite materials for the invention;

[0033] Figure 3 Analysis of the hydration dynamics diameter and charge of the iron-based composite material of this invention;

[0034] Figure 4 X-ray diffraction analysis was performed on the iron-based composite material prepared in this invention.

[0035] Figure 5 The diagram shows the SOD activity analysis of the iron-based composite material prepared in this invention.

[0036] Figure 6 The diagram shows the CAT activity analysis of the iron-based composite material prepared in this invention.

[0037] Figure 7 This is a graph showing the analysis of the antibacterial ability of the iron-based composite material prepared in this invention;

[0038] Figure 8 Scanning electron microscope image of the antibacterial activity of the iron-based composite material prepared in this invention;

[0039] Figure 9 This is a cytotoxicity analysis diagram of the iron-based composite material prepared in this invention;

[0040] Figure 10The present invention prepares iron-based composite materials to promote cell migration ability;

[0041] Figure 11 This is a schematic diagram illustrating the preparation of an iron-based composite material for the treatment of diabetic wounds according to the present invention;

[0042] Figure 12 This invention aims to prepare iron-based composite materials for the treatment of diabetic wounds;

[0043] Figure 13 This invention aims to develop an iron-based composite material for the treatment of diabetic infected wounds. Detailed Implementation

[0044] The technical solution of the present invention will be further described below with reference to the accompanying drawings.

[0045] Iron porphyrin, zirconium oxychloride octahydrate, benzoic acid, tannic acid, citric acid, sodium citrate, copper chloride, and N,N-dimethylformamide were all purchased from China National Pharmaceutical Group Co., Ltd. Xanthine, xanthine oxidase, and streptozotocin were purchased from Shanghai Yuanye Biotechnology Co., Ltd. Bacterial culture media (peptone, yeast extract, and agar powder) were all purchased from China National Pharmaceutical Group Co., Ltd. Cell culture media (PBS, CCK-8, and serum) were all purchased from Nanjing Shenghang Technology Co., Ltd.

[0046] The HUVEC endothelial cells were obtained from Wuhan Saiweier Biotechnology Co., Ltd.

[0047] Balb / c mice were obtained from Zhejiang Vital River Laboratory Animal Technology Co., Ltd.

[0048] Example 1: Preparation and Characterization of Iron-Based Composite Materials

[0049] according to Figure 1 The method shown describes the preparation of iron-based composite materials. The specific steps are as follows:

[0050] (1) Iron porphyrin, zirconium oxychloride octahydrate and benzoic acid were dissolved in N,N-dimethylformamide (DMF) at a mass ratio of 1:3:30, heated and stirred evenly; placed in an oil bath at 90 ℃ and stirred slowly for 5 h. After the reaction was completed, the mixture was cooled to room temperature and washed three times by centrifugation with DMF to obtain iron-based metal-organic framework nanozyme PCN-Fe.

[0051] (2) The iron-based metal-organic framework nanozyme PCN-Fe in step (1) was centrifuged to remove the supernatant, and then deionized water was added to disperse it to obtain an aqueous solution of PCN-Fe nanozyme. The aqueous solution of PCN-Fe nanozyme was stirred with a magnetic stirrer. After stirring evenly, tannic acid (TA) was added and stirring was continued for 30 minutes. The precipitate was collected by centrifugation and washed three times with deionized water to obtain the core-shell structure PCN-Fe@TA. The mass ratio of the aqueous solution of PCN-Fe nanozyme to tannic acid was 2:1.

[0052] (3) The core-shell structure PCN-Fe@TA co-loaded with Cu obtained in step (2) 2+ The specific steps are as follows: PCN-Fe@TA is dispersed in deionized water and stirred with a magnetic stirrer. After it is fully dispersed, copper dichloride (CuCl2) is added and stirred for more than 30 minutes until the solution turns dark brown. The precipitate is collected by centrifugation and washed three times with deionized water to obtain the iron-based composite material PCN-Fe@Cu. The mass ratio of PCN-Fe@TA aqueous solution to CuCl2 is 2:1.

[0053] Figure 2 Transmission electron microscope images of iron-based nanozymes and iron-based composite materials. Figure 3 Analysis of hydration dynamics diameter and charge in iron-based composite materials; Figure 4 X-ray diffraction analysis of iron-based composite materials.

[0054] Example 2 Activity Analysis of Iron-Based Composite Materials

[0055] (1) SOD-like activity analysis: The SOD-like activity of the iron-based composite material was measured using dihydroethidium as a fluorescent probe in O2. •− In the presence of DHE, it will be oxidized and produce a specific fluorescent signal. The degree of signal decrease reflects the material's removal of O2. •− The ability to produce O2 through the reaction of xanthine with xanthine oxidase. •−Weigh 2.3 mg of xanthine powder, add 300 μL of NaOH solution (1 M) and 700 μL of deionized water to dissolve it, obtaining a 15 mM xanthine solution, and store at 4 ℃ protected from light. Weigh 1 mg of xanthine oxidase (purchased specification 50 U / mg) and dissolve it in 5.95 mL of water to obtain an 8.4 U / mL xanthine oxidase solution, which is then placed in a brown centrifuge tube for later use. Add 840 μL of Tris-HCl buffer (0.1 M, pH=7.4), 20 μL of material solution (PCN-Fe and PCN-Fe@Cu prepared in Example 1 were prepared in concentration gradients of 0 μg / mL, 5 μg / mL, 10 μg / mL, 20 μg / mL and 40 μg / mL), 100 μL of xanthine solution (15 mM), and 20 μL of ethidium dihydrogen phosphate solution (5 mM, dissolved in DMSO) to a brown test tube and shake to mix. Finally, add 20 μL of xanthine oxidase solution (8.4 U / mL) to start the reaction. After incubation at 37 ℃ for 30 min, the fluorescence signal was measured with a grating set to 10 nm, an excitation wavelength of 470 nm, and a scanning wavelength of 500-700 nm. Figure 5 As shown, both PCN-Fe and PCN-Fe@Cu possess SOD-like enzyme activity, capable of catalyzing the generation of H2O2 from superoxide anions, and exhibit concentration-dependent SOD-like activity.

[0056] (2) CAT-like activity analysis: The CAT-like activity of the iron-based composite material was tested by a dissolved oxygen analyzer. The O2 content generated by the iron-based composite material in aqueous solution was determined by detecting the catalytic H2O2 generation. The concentration gradients of PCN-Fe and PCN-Fe@Cu prepared in Example 1 were the same as those tested above (the concentration gradients were 0 μg / mL, 5 μg / mL, 10 μg / mL, 20 μg / mL and 40 μg / mL, respectively). 60 μL of the material solution (the solutions PCN-Fe and PCN-Fe@Cu prepared in Example 1 with concentration gradients of 0 μg / mL, 5 μg / mL, 10 μg / mL, 20 μg / mL and 40 μg / mL, respectively) was added to 2640 μL of deionized water, mixed by blowing, and 300 μL of H2O2 solution (50 mM) was quickly added and timing was started. The dissolved oxygen analyzer reading was recorded every 15 s. Figure 5 As shown, both PCN-Fe and PCN-Fe@Cu exhibit concentration-dependent SOD-like activity, thus potentially suitable for subsequent anti-oxidative stress therapy. Figure 6 As shown, both PCN-Fe and PCN-Fe@Cu exhibit good CAT-like activity, effectively catalyzing the generation of O2 from H2O2, and their CAT-like activity also shows a concentration-dependent relationship.

[0057] based on Figure 5 and Figure 6 The results show that PCN-Fe and PCN-Fe@Cu form a cascade reaction by catalyzing the generation of H2O2 from superoxide anions through SOD-like activity and the generation of O2 from H2O2 through CAT-like activity, thus forming a strong antioxidant capacity.

[0058] Example 3: Analysis of the antibacterial ability of iron-based composite materials

[0059] (1) Antibacterial curve analysis: Staphylococcus aureus was added to the bacterial culture medium and shaken overnight at 37 ℃. The absorbance at 600 nm was measured using an enzyme-linked immunosorbent assay (ELISA) reader. 1 mL of bacterial culture was used to measure the OD value. 600 nm =1.0 Add to a 50 mL centrifuge tube, and then dilute with 49 mL of culture medium. Take 5 mL of the diluted bacterial culture and add 100 μL of PCN-Fe and PCN-Fe@Cu aqueous solutions at concentrations of 0.25 mg / mL, 0.5 mg / mL, 1 mg / mL, and 2 mg / mL, respectively. Then incubate in a shaking incubator, and every 4 h, take 200 μL and add it to a 96-well plate to measure the absorbance at 600 nm. Figure 7 As shown, the antibacterial curves of PCN-Fe and PCN-Fe@Cu are concentration-dependent, thus they can be used for subsequent wound antibacterial treatment.

[0060] (2) Scanning electron microscopy analysis of antibacterial activity: Staphylococcus aureus and the iron-based composite material were added to a 24-well plate and incubated for 12 h. After reaching a suitable growth density, glutaraldehyde was added and the plate was incubated overnight at 4 °C. The plate was then rinsed three times with 0.1 M PBS buffer and dried. Subsequently, it was soaked in 30%, 50%, 70%, 80%, 90%, and 100% ethanol solutions for 15 min each time. After the solutions evaporated, isoamyl acetate was added and the plate was soaked overnight. The slides were freeze-dried, sputter-coated with gold, and analyzed by scanning transmission electron microscopy. Figure 8 As shown, PCN-Fe and PCN-Fe@Cu have antibacterial capabilities, with PCN-Fe@Cu exhibiting stronger bactericidal activity, thus making it suitable for subsequent wound antibacterial treatment.

[0061] Example 4: Analysis of the Cell Protective Capacity of Iron-Based Composite Materials

[0062] (1) Cytotoxicity analysis: After resuscitation, HUVEC endothelial cells were centrifuged to remove the culture medium after reaching an appropriate density and recultured in DMEM high-glucose medium. After three passages, HUVEC cells were decanted using digestion solution and prepared into a cell suspension in DMEM high-glucose medium for counting. The cell suspension was added to 96-well plates at a volume of 100 μL per well and a cell density of 8000 cells / well. The plates were then transferred to a CO2 incubator for culture. After cell attachment, HUVEC cells were co-incubated with iron-based composite aqueous solutions of different concentration gradients for 24 h. After incubation, the culture medium was removed and the cells were washed three times with PBS solution (0.01 M, pH=7.4). Then, 100 μL of a detection solution prepared by 10 μL of CCK-8 solution and 90 μL of DMEM high-glucose medium was added to each well and incubated for 1.5 h. After incubation, the absorbance at 450 nm was measured using a microplate reader. Figure 9 As shown, PCN-Fe and PCN-Fe@Cu showed no significant cell-killing ability, indicating that the iron-based composite material has good biocompatibility, providing a basis for subsequent treatment of diabetic wounds.

[0063] (2) Cell Scratch Analysis: The resuscitation and culture process of HUVEC cells was the same as in step (1) above. Cells were cultured in a culture dish until the surface was completely covered. A sterile pipette tip was used to streak the cells perpendicular to the culture layer, followed by washing with PBS to remove floating cells. Cells were then recultured in DMEM high-glucose medium and co-incubated with aqueous solutions of PCN-Fe and PCN-Fe@Cu at concentrations of 40 μg / mL, respectively. After incubation in a CO2 incubator for 12 h, the culture dish was removed, and cell growth was observed under a microscope. Figure 10 As shown, PCN-Fe@Cu significantly promotes cell migration, providing a basis for subsequent treatment of diabetic wound healing.

[0064] Example 5: Therapeutic application of iron-based composite materials for diabetic wounds

[0065] Based on the preparation of iron-based composite materials, their therapeutic effects on diabetic wounds were explored, such as... Figure 11 As shown.

[0066] Preparation of streptozotocin: Solution A: Weigh 2.1 g of citric acid and dissolve in 100 mL of double-distilled water; Solution B: Weigh 2.94 g of sodium citrate (MW: 294.10) and dissolve in 100 mL of double-distilled water; Mix solutions A and B at a volume ratio of 1:1 and adjust the pH to between 4.2 and 4.5 to obtain a citrate-sodium citrate buffer solution, and pre-cool it at 4°C. Weigh 10 mg of streptozotocin and add it to 10 mL of citrate-sodium citrate buffer solution (pH=4.2-4.5) to obtain 1 mg / mL streptozotocin.

[0067] (1) Establishment of a diabetic mouse model: Balb / c mice were fasted for 24 h and then injected with 20 μL of streptozotocin solution at a concentration of 1 mg / mL via the tail vein. Blood glucose levels were monitored regularly using blood glucose test strips and a blood glucose monitor. The drug was administered again on the seventh day. The model was considered successfully established when the blood glucose level was ≥16.7 mmol / L.

[0068] (2) Wound modeling and treatment in diabetic mice: Wound modeling was performed on streptozotocin-induced diabetic mice, and hair removal cream was applied to the exposed area of ​​approximately 1 cm on the back. 2 Open wounds were created on the skin using scissors. Drugs were administered on days 1, 3, and 5, and the wounds were photographed and their area measured. The groups were as follows: negative control (non-diabetic mice), positive control (diabetic mice), PCN-Fe (diabetic mice treated with PCN-Fe at a dose of 5 mg / kg), and PCN-Fe@Cu (diabetic mice treated with PCN-Fe@Cu at a dose of 5 mg / kg). Figure 12 As shown, PCN-Fe@Cu can better promote wound healing.

[0069] (3) Infection modeling and treatment of diabetic mice: In streptozotocin-induced diabetic mice, wound modeling was performed, and hair removal cream was applied to the exposed area of ​​about 1 cm on the back. 2 The skin was used to create open wounds using scissors, and 50 μL of Staphylococcus aureus (LOD 600 nm = 1.0) was added. The drugs were administered on days 1, 3, and 5, and the wounds were photographed and their area measured. The groups were as follows: negative control (non-diabetic mice), positive control (diabetic mice), PCN-Fe (diabetic mice treated with PCN-Fe at a dose of 5 mg / kg), and PCN-Fe@Cu (diabetic mice treated with PCN-Fe@Cu at a dose of 5 mg / kg). Figure 13As shown, the iron-based composite material PCN-Fe@Cu, which integrates antibacterial, antioxidant stress, and angiogenesis properties, can better promote the healing of infected wounds. In summary, the iron-based composite material of this invention, PCN-Fe@Cu, formed by using an iron-based metal-organic framework nanozyme as the core, tannic acid as the shell modification, and co-loading copper ions, can effectively promote the treatment of wounds / wound infections in diabetic mice, providing a new approach to the treatment of diabetic wounds. This invention can be extended to other disease treatment applications by changing the type of iron-based nanozyme in the core, the modification layer of the shell, and other self-assemblies.

Claims

1. The application of an iron-based composite material in the preparation of drugs or reagents for improving and / or treating diabetic wounds, characterized in that, The iron-based composite material is PCN-Fe@Cu, wherein PCN-Fe@Cu is Cu co-loaded on a core-shell structure PCN-Fe@TA. 2+ It is found that the core-shell structure PCN-Fe@TA is obtained by adding tannic acid to the iron-based metal-organic framework nanoenzyme PCN-Fe for shell modification.

2. The application according to claim 1, characterized in that, The diabetic wounds include diabetic infected wounds.

3. The application according to claim 1, characterized in that, The preparation method of the iron-based composite material includes the following steps: (1) Iron porphyrin, zirconium oxychloride octahydrate and benzoic acid were dissolved in N,N-dimethylformamide, heated and stirred until homogeneous; the mixture was placed in an oil bath and stirred slowly. After the reaction was completed, the mixture was cooled to room temperature and washed with DMF by centrifugation to obtain iron-based metal-organic framework nanozyme PCN-Fe. (2) The supernatant of the nanozyme PCN-Fe was removed by centrifugation, and deionized water was added to disperse it to obtain an aqueous solution of PCN-Fe nanozyme; the aqueous solution of PCN-Fe nanozyme was stirred with a magnetic stirrer, and after being stirred evenly, TA was added and stirred again. The precipitate was collected by centrifugation and washed with deionized water to obtain the core-shell structure PCN-Fe@TA; (3) PCN-Fe@TA was dispersed in deionized water and stirred with a magnetic stirrer. After it was fully dispersed, copper dichloride was added and stirred until the solution turned dark brown. The precipitate was collected by centrifugation and washed with deionized water to obtain the iron-based composite material PCN-Fe@Cu.

4. The application according to claim 3, characterized in that, The mass ratio of iron porphyrin, zirconium oxychloride octahydrate and benzoic acid in step (1) is 1:3:30~1:3:

50.

5. The application according to claim 3, characterized in that, In step (1), the oil bath temperature is 90℃ and the reaction time is 5h.

6. The application according to claim 3, characterized in that, The mass ratio of PCN-Fe to tannic acid in step (2) is 2:1 to 5:

1.

7. The application according to claim 3, characterized in that, The concentration of PCN-Fe in step (2) is 5~40 μg / mL.

8. The application according to claim 3, characterized in that, The mass ratio of PCN-Fe@TA to CuCl2 in step (3) is 2:1 to 5:

1.

9. The application according to claim 3, characterized in that, The concentration of PCN-Fe@TA mentioned in step (3) is 5~40 μg / mL.

10. The application according to claim 1, characterized in that, The iron-based composite material is used to prepare drugs or preparations with antibacterial, antioxidant, and / or angiogenic properties.

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