Novel Antibacterial Agents With Synergistic Photothermal And Nanozyme Therapy For Bacterial Infection

Bacterial infection has become a major threat to human health in the world today.The traditional antibacterial means is to use antibiotics to kill bacteria.However,the long-term use of traditional antibiotics will not only lead to the decline of drug efficacy,but also lead to the continuous increase of bacterial resistance.Therefore,it is urgent to develop novel antimicrobial strategies that are less likely to produce drug resistance.In recent years,Nanozymes have been called a"new generation of antibiotics"due to their broad antibacterial properties and negligible biological toxicity.However,due to the inherent low catalytic activity,nanoenzyme therapy alone is unable to achieve more thorough sterilization,thus limiting its application in the antimicrobial field.In addition,Photothermal therapy（PTT）has high selectivity and is not easy to produce drug resistance by relying on local hyperthermic sterilization.However,excessive temperature will damage the normal tissues around the lesion,and only using mild Photothermal therapy to reduce side effects is not enough to completely kill the bacteria in the lesion.Based on the basic principle that temperature rise can accelerate the rate of chemical reaction,photothermal-nanozyme combination therapy is considered as a promising antimicrobial strategy.In addition,the biodegradation of antimicrobial agents is still a difficult problem,and the development of safer and more efficient combination antimicrobial agents is of great significance for the advance of antimicrobial work in the future.Therefore,we divided the main contents and conclusions of this paper into the following two parts:1)Biodegradable NiS_{2（）defined as ND}nanoparticles were prepared and used as a photothermal-nanozyme combined antimicrobial agent.The nanoparticles were prepared by a simple solvothermal reaction.The nanoparticles obtained have strong absorption and high photothermal conversion efficiency（43.8%）in the near infrared light region,and have excellent peroxidase-like catalytic activity.In the presence of hydrogen peroxide,the nanoparticles can catalyze the generation of hydroxyl radical（·OH）from H₂O₂.Under the irradiation of near-infrared light,the mild photoheat generated by the nanoparticles can promote its catalytic activity to achieve photothermal enhanced antimicrobial therapy of nanozymes.In addition,the nanoparticles act as a glutathione peroxidase mimicase（GSH-Px）,enhancing the antimicrobial effect by consuming GSH inside the bacteria.The antibacterial study of mouse wound infection model showed that the photothermal-nanozyme synergistic antibacterial effect of the nanoparticles could significantly kill the bacteria in the wound area and was conducive to wound healing.In addition,metabolic studies in mice showed that the nanoparticles could be quickly cleared by excretion,which confirmed the excellent biodegradability and safety of the materials.2)Copper single atom/nitrogen-doped porous carbon（CuSASs/NPC,defined as:Cu/NPC）nanoparticles were prepared.The synthesis of the nanoparticles consisted of four steps:pyrolysis,etching,adsorption and pyrolysis,which could be used for photothermal-nanozyme combined antimicrobial therapy.Cu/NPC nanoparticles have excellent peroxidase-like catalytic activity,GSH consumption function and photothermal properties.In the presence of hydrogen peroxide,the nanoparticles can induce the production of·OH by means of peroxidase activity,which not only achieves a certain degree of bactericidal effect,but also enhances the sensitivity of bacteria to thermal damage.When near-infrared light is introduced,the nanoparticles produce mild photoheat to kill bacteria and enhance the catalytic activity of peroxidase-like enzymes to produce more·OH for sterilization.In addition,the GSH consumption function of the nanoparticles can further enhance the antibacterial effect of the materials.In vitro antibacterial studies showed that the synergistic antibacterial rate of photothermal-nanozyme was close to 100%against Escherichia coli and methicillin-resistant Staphylococcus aureus.The antibacterial study of mouse wound infection model showed that the material had obvious killing effect on the bacteria at the infected site and could significantly improve the healing of the infected wound.