Modified Ti3C2TX MXene hydrogel material for enhancing photo-thermal antibiosis by releasing NO under excitation of H2O2
By preparing H2O2 to stimulate the release of NO, the modified Ti3C2TX MXene hydrogel material combined with photothermal therapy and NO release, the problems of bacterial infection and oxidative stress in chronic wound treatment were solved, and efficient antibacterial and antioxidant properties were achieved to promote wound healing.
Patent Information
- Application Number
- CN202510626465.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-15
- Publication Date
- 2025-08-08
AI Technical Summary
The prior art is difficult to effectively control bacterial infection and prolong inflammation caused by hyperoxidant stress in chronic wound treatment, affecting wound healing.
By preparing H2O2-excited and releasing NO, the modified Ti3C2TX MXene hydrogel material is used to stimulate the release of NO, combining photothermal therapy and NO release to enhance antibacterial performance, using MXene@TiO2 nanoparticles to improve stability and antioxidant performance, loading L-Arg as the NO donor to achieve low-level H2O2-triggered NO release.
Under near-infrared light, the material significantly enhances the killing effect of Gram-positive and negative bacteria through the synergistic effect of photothermal and NO release, promotes wound healing, reduces the risk of secondary infection, and has excellent antioxidant properties and biocompatibility.
Smart Images
Figure CN120437368A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of biomedical materials, and specifically relates to a modified Ti3C2T3 with H2O2 excitation to release NO and enhance photothermal antibacterial properties. X MXene hydrogel materials. Background Art
[0002] With the aging of the global population and the increasing prevalence of diabetes and other health problems, more and more patients are experiencing chronic wounds. Skin wound repair and reconstruction requires a complex and lengthy self-healing process, including blood coagulation, inflammation, cell proliferation, and wound contraction and remodeling. During this process, disinfectants and antibiotics are frequently used to inhibit bacterial infection and complications. However, excessive use of antibiotics may lead to bacterial multidrug resistance, which can cause life-threatening infections in severe cases. Therefore, the development of new antibacterial materials and antibacterial therapies is extremely urgent.
[0003] MXene is an emerging 2D multifunctional, ultrathin nanomaterial with excellent photothermal and catalytic properties under near-infrared irradiation, as well as excellent biocompatibility. It is a promising candidate for drug-free antimicrobial therapy and holds great promise for application in biomedical engineering. However, MXene's susceptibility to oxidation and difficulty in preservation hinder its widespread adoption. In situ growth of TiO2 nanoparticles (NPs) on its surface can enhance its stability and antioxidant properties, extending its shelf life. This method also addresses the aggregation and stacking issues between MXene layers and eliminates sharp edges, improving both performance and bioactivity.
[0004] Nitric oxide (NO), an endogenous gaseous molecule crucial for pathophysiological and physiological processes, is a promising broad-spectrum antimicrobial agent. Unlike traditional antimicrobial agents, low concentrations of NO (<1.0 μM) promote wound regeneration through multiple mechanisms, including increased myofibroblasts, collagen deposition, and wound contraction. The combination of NO and photothermal therapy can not only effectively reduce the risks of local hyperthermia but also promote tissue regeneration.
[0005] The MAX phase (Ti3AlC2) was peeled off to form multilayer Ti3C2T by hydrochloric acid etching. XMXene is then prepared by a hydrothermal method to obtain MXene@TiO2, which not only gives the hydrogel excellent near-infrared response photothermal antibacterial properties, but also exhibits excellent antioxidant activity. On this basis, MXene / MXene@TiO2 and L-Arg are prepared into hydrogels, and low levels of H2O2 are used to trigger the release of NO by reacting with L-Arg, which can further improve the antibacterial efficiency, trigger macrophages to defend against infection, stimulate angiogenesis, and induce skin organ regeneration, thereby promoting the wound healing process. This concept has rarely been reported in the field of biomedical materials technology. In view of this, the present invention provides a modified Ti3C2T with H2O2 excitation to release NO to enhance photothermal antibacterial properties. X MXene hydrogel materials. Summary of the Invention
[0006] The purpose of this invention is to address the problem of prolonged inflammation and impaired wound healing due to the harmful effects of uncontrolled bacterial infection and excessive oxidative stress in the treatment of infected wounds in clinical practice. A modified Ti3C2T3 with H2O2-triggered NO release and enhanced photothermal antibacterial performance is proposed. X MXene hydrogel material. This coating can enhance the antibacterial and antioxidant properties of titanium-based implants, improving their biocompatibility. Furthermore, short-term 808nm NIR irradiation of the hydrogel surface controls the temperature to rise from 24.6°C to 48.0°C, a temperature that does not cause significant damage to human tissue.
[0007] The MAX phase (Ti3AlC2) was peeled off to form multilayer Ti3C2T by hydrochloric acid etching. X MXene was then prepared by a hydrothermal method to obtain MXene@TiO2. MXene / MXene@TiO2 and the NO donor L-Arg were then loaded into the hydrogel to finally prepare a sustainable wound healing system, and the release of NO was triggered by low levels of H2O2. This system gave the hydrogel excellent antibacterial properties, and the materials used were all non-toxic, giving it excellent antioxidant properties. Overall, this trigger for sustainable wound healing, with its synergistic antibacterial activity, was established for wound healing and disinfection.
[0008] The present invention is specifically achieved through the following technical solutions:
[0009] A modified Ti3C2T3O2 with H2O2-activated NO release for enhanced photothermal antibacterial properties XThe MXene hydrogel material is characterized in that the hydrogel material is constructed from a degradable hydrogel dressing, MXene and MXene@TiO2 with excellent photothermal and antioxidant properties, a biosafe NO donor L-Arg, and a low level of H2O2. The hydrogel material has stable photothermal conversion capabilities under short-term irradiation with 808nm near-infrared light and the ability to promote NO release under low-level H2O2 triggering. The synergistic effects of photothermal and NO release can enhance the antibacterial ability of the material, and it exhibits good L929 cell biocompatibility and excellent antioxidant capacity. The modified Ti3C2T X The preparation method of MXene hydrogel material comprises the following steps:
[0010] (1) Preparation of multilayer MXene: LiF and hydrochloric acid solution were added to a polytetrafluoroethylene container and ultrasonically mixed. The MAX phase (Ti3AlC2) was slowly added to the mixed solution. The mixture was then wrapped in plastic wrap, punctured with a needle, and placed in a water bath for reaction. After the reaction was complete, the mixture was washed with deionized water by centrifugation several times, then dried and removed for later use.
[0011] (2) Hydrothermal treatment: The multilayer Ti3C2T x MXene and NaBF4 were added to an HCl solution and stirred for 20 minutes before being transferred to a polytetrafluoroethylene (PTFE)-lined stainless steel autoclave for hydrothermal treatment. After the reaction, the mixture was washed with ethanol and deionized water by centrifugation multiple times before being dried and removed for later use.
[0012] (3) Preparation of TSPBA: TMPDA and 4-BPBA were dissolved in dimethylformamide with continuous heating and stirring. The solution was poured into tetrahydrofuran to precipitate the product. The precipitate was washed three times with tetrahydrofuran and dried in vacuum overnight to obtain TSPBA.
[0013] (4) Synthesis of hydrogel: PVA was dissolved in deionized water, and the solution was filtered through a cellulose acetate filter membrane. The TSPBA obtained in step (3) was dissolved in deionized water. The two precursor solutions of equal volume were mixed, and before gelation, the MXene obtained in step (1), the MXene@TiO2 obtained in step (2), and L-Arg were dissolved in the PVA precursor solution according to the experimental requirements. Thus, the modified Ti3C2T3O2 with enhanced photothermal antibacterial properties by H2O2 excitation and NO release was obtained. X MXene hydrogel materials.
[0014] Furthermore, the concentration of hydrochloric acid in step (1) is 7 to 12 M; and the hydrothermal reaction temperature in step (1) is 30 to 55°C.
[0015] Furthermore, the concentration of the hydrochloric acid solution in step (2) is 1 to 4 M; the hydrothermal working temperature in step (2) is 100 to 300° C., and the reaction time is 12 to 48 hours.
[0016] Furthermore, the stirring heating temperature of step (3) is 60 to 80° C.; and the stirring time of step (3) is 12 to 24 hours.
[0017] Beneficial effects
[0018] The beneficial effects of the present invention are:
[0019] (1) The hydrogel material has excellent antibacterial properties and has a good killing effect on both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), reducing the risk of secondary infection of wounds. Moreover, under near-infrared light irradiation, controlling the temperature of the hydrogel in vitro will not cause significant damage to human tissue. On the basis of photothermal response, the synergistic release of NO can effectively inhibit the formation of bacterial biofilms.
[0020] (2) TiO2 nanoparticles (NPs) grown in situ on the MXene surface can enhance its stability and antioxidant properties. Under near-infrared light irradiation, the photothermal conversion efficiency is high and it has stable antibacterial activity. At the same time, it extends its shelf life and solves the inevitable aggregation and stacking problems between MXene layers, thereby improving performance. Eliminating the sharp edges of MXene will also have a negative impact on normal cells, resulting in increased biological activity.
[0021] (3) NO is an endogenous gaseous molecule that can penetrate deep into biofilms to destroy DNA and proteins and produce reactive nitrogen for bacterial inactivation. The synergistic mild photothermal effect achieves enhanced bactericidal activity, which together helps to induce the spread of biofilms and the destruction of bacterial plasma membranes, which further leads to the leakage and damage of intracellular components, resulting in bacterial inactivation and ultimately the elimination of biofilms.
[0022] (4) The hydrogel material has a simple structure, low cost, is easy to prepare, and has universal applicability. BRIEF DESCRIPTION OF THE DRAWINGS
[0023] In order to make the purpose, technical solutions and beneficial effects of the present invention more clear, the present invention provides the following drawings for illustration:
[0024] Figure 1 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 1 X Summary image of MXene hydrogel materials.
[0025] Figure 2 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 1 XSEM image of MXene hydrogel material (MXene).
[0026] Figure 3 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 1 X MXene hydrogel material (MXene) and control group under near-infrared irradiation (λ = 808 nm, 1 W / cm 2 ) photothermal heating curve.
[0027] Figure 4 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 2 X XRD pattern of MXene@TiO2 of MXene hydrogel material.
[0028] Figure 5 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 2 X L929 cytotoxicity of MXene hydrogel materials (MXene).
[0029] Figure 6 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 3 X Antibacterial effect of MXene hydrogel material (Hydrogel / Hydrogel+H2O2) and control group against Gram-positive bacteria (Staphylococcus aureus).
[0030] Figure 7 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 3 X NO concentration released by MXene hydrogel material (Hydrogel) and control group under different conditions.
[0031] Figure 8 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 3 X Evaluation of the antioxidant activity of MXene hydrogel material (Hydrogel) and control group. DETAILED DESCRIPTION
[0032] Example 1
[0033] (1) Preparation of multilayer MXene: Weigh a certain amount of lithium fluoride and 9M hydrochloric acid solution into a polytetrafluoroethylene container and mix ultrasonically. Slowly add the MAX phase (Ti3AlC2) to the mixed solution, then wrap it in plastic wrap, poke several holes with a needle, and place it in a water bath at 45°C for 24 hours. After the reaction is complete, wash it with deionized water by centrifugation several times, then dry it and remove it for use.
[0034] (2) Hydrothermal treatment: The multilayer Ti3C2T x MXene and NaBF4 were added to a 1M HCl solution and stirred for 20 minutes. The mixture was then transferred to a polytetrafluoroethylene (PTFE)-lined stainless steel autoclave for hydrothermal treatment at 180°C for 36 hours. After the reaction, the mixture was washed by centrifugation with ethanol and deionized water multiple times, then dried and removed for later use.
[0035] (3) Preparation of TSPBA: TMPDA and 4-BPBA were dissolved in dimethylformamide and heated at 60°C with stirring for 12 h. The solution was poured into tetrahydrofuran to precipitate the product. The precipitate was washed three times with tetrahydrofuran and dried in vacuum overnight to obtain TSPBA.
[0036] (4) Synthesis of hydrogel: PVA was dissolved in deionized water, and the solution was filtered through a cellulose acetate filter membrane. The TSPBA obtained in step (3) was dissolved in deionized water. The two precursor solutions of equal volume were mixed, and before gelation, the MXene obtained in step (1) was dissolved in the PVA precursor solution according to the experimental requirements. The modified Ti3C2T3O2 was obtained, which released NO under H2O2 excitation and enhanced photothermal antibacterial properties. X MXene hydrogel material. Note: MXene.
[0037] Figure 1 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 1 X Summary image of MXene hydrogel materials. Figure 2 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 1 X SEM image of MXene hydrogel material (MXene). Figure 3 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 1 X MXene hydrogel material (MXene) and control group under near-infrared irradiation (λ = 808 nm, 1 W / cm 2 )’s photothermal heating curve, the MXene hydrogel has a significant temperature increase compared to the control group.
[0038] Example 2
[0039] (1) Preparation of multilayer MXene: Weigh a certain amount of lithium fluoride and 9M hydrochloric acid solution into a polytetrafluoroethylene container and mix ultrasonically. Slowly add the MAX phase (Ti3AlC2) to the mixed solution, then wrap it in plastic wrap, poke several holes with a needle, and place it in a water bath at 45°C for 24 hours. After the reaction is complete, wash it with deionized water by centrifugation several times, then dry it and remove it for use.
[0040] (2) Hydrothermal treatment: The multilayer Ti3C2T x MXene and NaBF4 were added to a 1M HCl solution and stirred for 20 minutes. The mixture was then transferred to a polytetrafluoroethylene (PTFE)-lined stainless steel autoclave for hydrothermal treatment at 180°C for 24 hours. After the reaction, the mixture was washed by centrifugation with ethanol and deionized water multiple times, then dried and removed for later use.
[0041] (3) Preparation of TSPBA: TMPDA and 4-BPBA were dissolved in dimethylformamide and heated at 60°C with stirring for 12 h. The solution was poured into tetrahydrofuran to precipitate the product. The precipitate was washed three times with tetrahydrofuran and dried in vacuum overnight to obtain TSPBA.
[0042] (4) Synthesis of hydrogel: PVA was dissolved in deionized water, and the solution was filtered through a cellulose acetate filter membrane. The TSPBA obtained in step (3) was dissolved in deionized water. The two precursor solutions of equal volume were mixed, and before gelation, the MXene@TiO2 obtained in step (1) was dissolved in the PVA precursor solution according to the experimental requirements. The modified Ti3C2T X MXene hydrogel material. Note: MXene@TiO2.
[0043] Figure 4 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 2 X XRD pattern of MXene@TiO2 of MXene hydrogel material. Figure 5 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 2 X The L929 cell toxicity of MXene hydrogel material (MXene) and the relative proliferation rate of L929 cells co-cultured with MXene hydrogel were all around 100%, indicating no cytotoxicity.
[0044] Example 3
[0045] (1) Preparation of multilayer MXene: Weigh a certain amount of lithium fluoride and 9M hydrochloric acid solution into a polytetrafluoroethylene container and mix ultrasonically. Slowly add the MAX phase (Ti3AlC2) to the mixed solution, then wrap it in plastic wrap, poke several holes with a needle, and place it in a water bath at 45°C for 24 hours. After the reaction is complete, wash it with deionized water by centrifugation several times, then dry it and remove it for use.
[0046] (2) Hydrothermal treatment: The multilayer Ti3C2T xMXene and NaBF4 were added to a 1M HCl solution and stirred for 20 minutes. The mixture was then transferred to a polytetrafluoroethylene (PTFE)-lined stainless steel autoclave for hydrothermal treatment at 180°C for 12 hours. After the reaction, the mixture was washed by centrifugation with ethanol and deionized water multiple times, then dried and removed for later use.
[0047] (3) Preparation of TSPBA: TMPDA and 4-BPBA were dissolved in dimethylformamide and heated at 60°C with stirring for 12 h. The solution was poured into tetrahydrofuran to precipitate the product. The precipitate was washed three times with tetrahydrofuran and dried in vacuum overnight to obtain TSPBA.
[0048] (4) Synthesis of hydrogel: PVA was dissolved in deionized water, and the solution was filtered through a cellulose acetate filter membrane. The TSPBA obtained in step (3) was dissolved in deionized water. The two precursor solutions of equal volume were mixed, and before gelation, the MXene@TiO2 and L-Arg obtained in step (1) were dissolved in the PVA precursor solution according to the experimental requirements. Thus, the modified Ti3C2T3O2 with enhanced photothermal antibacterial properties by H2O2 excitation and NO release was obtained. X MXene hydrogel material. If no H2O2 is added, it is denoted as Hydrogel; if H2O2 is added, it is denoted as Hydrogel+H2O2.
[0049] Figure 6 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 3 X The antibacterial effect of MXene hydrogel material (Hydrogel / Hydrogel+H2O2) and the control group on Gram-positive bacteria (Staphylococcus aureus) is shown. Without NIR irradiation, the control group had no inhibitory effect on Staphylococcus aureus. The antibacterial efficiency of the Hydrogel sample against Staphylococcus aureus reached 21.3%, and the antibacterial efficiency of the Hydrogel+H2O2 sample against Staphylococcus aureus reached 69.6%. Under NIR irradiation treatment (λ=808nm, T=48℃), the antibacterial efficiencies of Hydrogel and Hydrogel+H2O2 against Staphylococcus aureus reached 60.8% and 94.8%, respectively. Figure 7 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 3 X The NO concentration released by MXene hydrogel material (Hydrogel) and the control group under different conditions can be observed. Hydrogel can continuously release NO under low levels of H2O2. Figure 8 The modified Ti3C2T3 that releases NO by H2O2 excitation to enhance photothermal antibacterial in Example 3 XEvaluation of the antioxidant activity of MXene hydrogel material (Hydrogel) and the control group showed that the hydrogel has excellent antioxidant capacity.
[0050] Obviously, the above-mentioned Examples 1, 2, and 3 of the present invention are merely examples for the purpose of clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art will be able to make other variations or modifications based on the above descriptions. It is not necessary and impossible to enumerate all embodiments here. However, these obvious variations or modifications derived from the spirit of the present invention remain within the scope of protection of the present invention.
Claims
1. A modified Ti3C2T3 with H2O2-stimulated NO release for enhanced photothermal antibacterial properties X MXene hydrogel material, characterized in that The hydrogel material is constructed from a degradable hydrogel dressing, MXene and MXene@TiO2 with excellent photothermal and antioxidant properties, a biosafe NO donor L-Arg, and a low level of H2O2. The hydrogel material has stable photothermal conversion capabilities under short-term irradiation with 808nm near-infrared light and the ability to promote NO release under low-level H2O2 triggering. The synergistic effects of photothermal and NO release can enhance the antibacterial ability of the material, and it exhibits good L929 cell biocompatibility and excellent antioxidant capacity. The modified Ti3C2T X The preparation method of MXene hydrogel material comprises the following steps: (1) Preparation of multilayer MXene: LiF and hydrochloric acid solution were added to a polytetrafluoroethylene container and ultrasonically mixed. The MAX phase (Ti3AlC2) was slowly added to the mixed solution. The mixture was then wrapped in plastic wrap, punctured with a needle, and placed in a water bath for reaction. After the reaction was complete, the mixture was washed with deionized water by centrifugation several times, then dried and removed for later use. (2) Hydrothermal treatment: The multilayer Ti3C2T x MXene and NaBF4 were added to an HCl solution and stirred for 20 minutes before being transferred to a polytetrafluoroethylene (PTFE)-lined stainless steel autoclave for hydrothermal treatment. After the reaction, the mixture was washed with ethanol and deionized water by centrifugation multiple times before being dried and removed for later use. (3) Preparation of TSPBA: TMPDA and 4-BPBA were dissolved in dimethylformamide with continuous heating and stirring. The solution was poured into tetrahydrofuran to precipitate the product. The precipitate was washed three times with tetrahydrofuran and dried in vacuum overnight to obtain TSPBA. (4) Synthesis of hydrogel: PVA was dissolved in deionized water, and the solution was filtered through a cellulose acetate filter membrane. TSPBA obtained in step (3) was dissolved in deionized water. Equal volumes of the two precursor solutions were mixed. Before gelation, the MXene obtained in step (1), the MXene@TiO2 obtained in step (2), and L-Arg were dissolved in the PVA precursor solution according to experimental requirements.
2. The modified Ti3C2T3 with H2O2 excitation to release NO and enhance photothermal antibacterial properties according to claim 1 X The preparation method of MXene hydrogel material is characterized in that: The hydrochloric acid concentration in step (1) is 7-12M, and the hydrothermal temperature of the reaction is 30-55°C.
3. The modified Ti3C2T3 with H2O2 excitation to release NO and enhance photothermal antibacterial properties according to claim 1 X The preparation method of MXene hydrogel material is characterized in that: The concentration of the hydrochloric acid solution in step (2) is 1 to 4 M; the hydrothermal working temperature in step (2) is 100 to 300° C., and the reaction time is 12 to 48 hours.
4. The modified Ti3C2T3 with H2O2 excitation to release NO and enhance photothermal antibacterial properties according to claim 1 X The preparation method of MXene hydrogel material is characterized in that: The stirring heating temperature of the step (3) is 60 to 80° C.; the stirring time of the step (3) is 12 to 24 hours.