Applications Of Functional Nanomaterials In Bactericidal Field

The development of nanomaterials provides a new strategy for the development of antimicrobial drugs.Nanomaterials can selectively kill bacteria,target bacterial infection sites,increase drug enrichment,and reduce cytotoxicity or side effects.Although nanomaterials have excellent antibacterial properties and are now in various the stage of clinical trials,which are promising and exciting,they are still some difficulties and challenges including biocompatibility and selectivity,mechanistic understanding and animal model studies.To solve those problems,the development of new functional antibacterial nanomaterials and explore the antibacterial mechanism is urgent.In this dissertation,a brief review of the previous works on the developments nanoparticles is presented.We then prepared functionalized nanoparticles and characterized their properties.Based on those,bactericidal performance of functionalized nanoparticles were carried out:1.Nanoparticle Coated with Extracellular Vesicle Membrane of Staphylococcus aureus is Used as the Carrier of Active Targeted Transport for Eradication of Intracellular Bacterial Infection.In worldwide,bacteremia caused by Staphylococcus aureus is one of the most serious bacterial infections.Most complications of S.aureus bacteremia arise because the pathogen can survive inside host phagocytes,especially macrophages,which makes elimination of intracellular S.aureus key to clinical success.Unfortunately,most antibiotics have poor cellular penetration capacity,which necessitates intracellular delivery of antibiotics.We herein use nanoparticle coated with membrane of extracellular vesicle secreted by S.aureus(i.e.,NP@EV)as active-targeting antibiotic carrier.NP@EV is internalized at higher efficiency by S.aureus-infected macrophage and enhanced antibiotics efficiency.When injected intravenously into mouse models,NP@EV exhibits significantly higher accumulations within four major organs(kidney,lung,spleen,and heart)bearing metastatic S.aureus infections.As a result,when preloaded with antibiotics and intravenously administered to alleviate metastatic infection in S.aureus bacteremia-bearing mouse model,Moreover,simply by switching its coating from the membrane of S.aureus EV to that of E.coli OMV,the resulting NP@OMV acquires active targeting to E.coli infected macrophage,indicating that our delivery system is readily adaptable depending on which specific intracellular pathogen is to be eliminated.2.Oxidase-like Metal and Alloy Nanoparticles Kill Preferentially Bacteria over Host cells and Inhibit Biofilm Formation.Nanoenzymes capable of catalyzing the generation of reactive oxygen species(ROS)eliminate antibiotic-resistant bacteria while delaying the onset of resistance emergence after repeated treatment Unfortunately,under normal conditions,ROS cannot distinguish bacteria from mammalian cells.We herein propose oxidase-like metal and alloy nanoparticles to kill preferentially bacteria over mammalian cells and inhibit the formation of biofilms.Using oxidase-like AgPd bimetallic alloy nanocage,we demonstrated experimentally that it generates surface-bound ROS that are as reactive as 1O2 and kills preferentially bacteria over mammalian cells in vitro and promoted wound disinfection without off-target toxicity in mouse models.Notably,the surface-bound nature of the ROS on AgPd nanocage did not impact its potency in killing antibiotic-resistant bacteria or in delaying the onset of bacterial resistance emergence,suggesting potential for addressing genetically encoded resistance.Moreover,coating a substrate with AgPd enabled the as-modified surface to inhibit biofilm formation both in vitro and in mouse models.Thermal reduced TiO2 nanoparticle unanimously exhibited preferential killing of bacteria over mammalian cells,despite of the distinction in their materials and in ROS types they generate.Such a strong similarity in bioactivity despite of their distinction in materials encouraged us to propose that preferential killing of bacteria over mammalian cells is a global behavior for nanoparticles that spontaneously generate surface-bound ROS.This work opens an avenue toward biocompatible nanozymes and identifies its new mechanism,which suggests oxidase-like metal and alloy nanomaterials as biocompatible coating additives can inhibit biofilm formation,and realize effect of against both genetically-encoded and phenotypic AMR.