Preparation Of Biomimetic Dual-nanozymes Modified With Amino Acid And Their Antibacterial Application

Bacterial infections could cause various diseases and pose a serious threat to human health.The excessive use of antibiotics leads to the production of drug-resistant bacteria,which greatly reduces the efficacy of antibiotics.Moreover,bacterial infections are mostly caused by biofilms,and extracellular polymers in biofilms also prevent the penetration of antibiotics and increase bacterial resistance.In recent years,a variety of new nanomaterial antibacterial agents have been developed and studied.Among them,the nanozymes with the capability of producing reactive oxygen species for antibacterial have many advantages.Nanozyme has excellent catalytic performance and does not require external field assistance.The reactive oxygen species have good membrane permeability,could have a broad-spectrum antibacterial effect,and are not easy to cause drug resistance.Nanozymes contain special nanostructures and properties,and their catalytic performance could be regulated by adjusting their components,interactions between components,morphology,and size.Nanozymes could also be modified to give them more excellent properties and a variety of antibacterial strategies to enhance antibacterial effects.In this paper,the antibacterial materials of double nanozymes were first prepared,and reactive oxygen species were produced by catalytic cascade reaction to achieve antibacterial activity.On this basis,cationic amino acids were further modified to synergistically enhance the antibacterial effect.In the second chapter,Fe-based nanoshuttle FeOOH@Fe-Serine was prepared by hydrolysis of Fe³⁺and coordination with amino acids,and gold nanoparticles were loaded on the surface of FeOOH@Fe-Serine to construct a double nanozyme FeOOH@Fe-Serine@Au.The gold nanoparticles with glucose oxidase-like activity and the divalent iron with peroxidase-like activity showed good catalytic performance.The cascade catalytic reaction promotes the production of hydroxyl radicals using non-toxic glucose,and achieves effective antibacterial activity.In the diabetic wound infected by Staphylococcus aureus,the gold nanoparticles could maximize their glucose oxidase-like activity by utilizing the high concentrations of glucose and weak alkali environment characteristics of chronic wounds to produce gluconic acid and hydrogen peroxide.The consumption of glucose and the creation of an acidic environment inhibit the growth of bacteria at the wound.At the same time,the acidic environment could also improve the peroxidase-like activity of FeOOH@Fe-Serine@Au,which produces a large amount of hydroxyl radicals to achieve antibacterial activity.In addition,FeOOH@Fe-Serine@Au accelerates the healing of the diabetic wounds by reducing the inflammation level and promoting angiogenesis after antibacterial treatment.In cell and animal experiments,FeOOH@Fe-Serine@Au has not shown any signs of toxicity effects and adverse reactions in vivo or in vitro.In the third chapter,lysine aggregates modified nanoshuttle FeOOH@Fe-Lysine were prepared by the coordination of positively charged and biocompatible lysine with Fe³⁺and hydrolysis of Fe³⁺.The positive FeOOH help FeOOH@Fe-Lysine adhere to bacteria,and further destroy the bacterial membrane by lysine aggregates similar to polylysine antimicrobial peptide,which showed obvious antibacterial effect on planktonic methicillin-resistant Staphylococcus aureus and ampicillin-resistant Escherichia coli.Then,gold nanoparticles were loaded on the surface of FeOOH@Fe-Lysine to prepare double nanozyme FeOOH@Fe-Lysine@Au.The production of hydroxyl radicals through cascade catalytic reactions by FeOOH@Fe-Lysine@Au could enhance the antibacterial properties of planktonic drug-resistant bacteria and biofilms.In diabetic wounds infected by drug-resistant bacteria,FeOOH@Fe-Lysine@Au has an antibacterial effect of more than 99%through the aggregation modification of lysine and the cascade catalysis of nanozymes,thereby promoting wound healing.Meanwhile,because FeOOH@Fe-Lysine also has a certain antibacterial effect,it also promotes wound healing compared with the control group.During the treatment of diabetic wounds,both FeOOH@Fe-Lysine and FeOOH@Fe-Lysine@Au showed good biosafety.In the fourth chapter,FeOOH@Fe-Lysine@Au exhibits excellent glucose oxidase-like activity,peroxidase-like activity and cascade catalytic performance under the acidic conditions of cariogenic biofilm.In the cariogenic biofilm rich in glucose,the cascade catalytic reaction of FeOOH@Fe-Lysine@Au could be activated and catalyze glucose to produce hydroxyl radicals.At the same time,the generated hydroxyl radicals could degrade the extracellular polymer and expose the internal bacteria,and then cooperate with the lysine aggregates to damage the bacterial membrane,affecting the ribosomal protein synthesis and metabolism processes to achieve antibacterial activity.In the dental caries model of organisms,FeOOH@Fe-Lysine@Au effectively prevents enamel damage and tooth cavitation by removing the cariogenic biofilm on the molars.In addition,FeOOH@Fe-Lysine@Au also has good biocompatibility and does not affect the bacterial diversity of the oral and intestinal environment.