Preparation And Antibacterial Applications Of Novel Silver Nanoparticles

Infection induced by bacteria,one of the most ticklish health problems globally,resulted in millions of illnesses each year.The biofilm related formation in the body is considered as one of the major reasons for sustained bacterial infections,which making them tolerant to conventional antibiotics and even induce the development of multidrug resistance(MDR)strains through metabolic dormancy and blocking antibacterial agents penetration into the biofilm.Antibacterial nanoparticles(NPs)have been used as substitutes to conventional antibiotics to fight against the development of MDR due to different antibacterial mechanisms and multiple modes of action of these nanoparticles.Silver nanoparticles have been widely applied in medicine owing to its high antimicrobial activity and limited bacterial resistance.However,the side-effects of silver nanoparticles to mammalian cells and cannot penetrate the full depth of mature bacteria biofilm,which limits its further application in the field of biomedicine.To overcome severe biofilm infections,the modified silver nanoparticles were treated from two aspects in this study.Firstly,based on the powerful antimicrobial activities of silver nanoparticles while problems do exist with relatively high cytotoxicity and poor permeability to biofilm.Using the microenvironments of the bacterial infection sites and normal tissues are differences,such as lower pH,high expression of some special enzymes,hydrogen peroxide and released toxins,etc.,silver nanoparticles with surface charge switchable activities were desided and achieved the purpose of improving the compatibility and bactericidal activity.Moreover,the zwitterion modified AgNPs were found excellent penetration into the matured biofilms and killed the microorganisms reside in the biofilm performance.Secondly,cationic silver nanoparticles were prepared by using polymer polyethylenimine(PEI)as surface modifier and stabilizer.And on this basis multilayer membranes(HA/PEI-AgNPs)with antifouling and bactericidal functions were designed based on positively charged silver nanoparticles(PEI-AgNPs)and hyaluronic acid(HA)by using layer-by-layer assembly method to prevent the formation of bacterial biofilm.Above all,silver nanoparticles were used as the antibacterial agent and modified on the surface.From the two aspects of killing mature bacterial biofilm to preventing the formation of biofilms to solve the problem of chronic periodic infections.The concrete work was as follows:(1)In order to decrease the cytotoxity of silver nanoparticles to mammalian cells while increase their antibacterial and antibiofilm efficiency.We prepared a novel nanocomposite composed of silver nanoparticles decorated with carboxyl betaine(CB)groups(AgNPs-LA-OB).The zwitterion modified AgNPs showed pH-responsive transition from negative charge to positive charge,which confer the zwitterionic nanocomposites biocompatible to mammalian cells and red blood cells in healthy tissues(pH?7.4),while pronounced bacteria binding of cationic nanocomposites at an bacterial infectiou site(pH?5.5)based on electrostatic attraction.The AgNPs penetrated deeply into bacterial biofilms and killed the resided bacteria in an acidic environment.The results indicated promising capability of the designed zwitterion nanoparticles for antibacterial applications and eradication of bacterial biofilms while the particles were compatible with the healthy cells.The satisfactory selectivity for bacteria compared to RBCs,together with their potent biofilm elimination activities make the designed zwitterion coated silver nanoparticles as a promising candidate antibacterial agent for fighting bacterial infection in biological medical field.(2)In order to solve severe biofilm infections,the first strategy is to kill mature biofilm structures and prevent the disease getting worse.Another common strategy is rely on prevent bacterial adhesion and thus inhibit biofilm formation.AgNPs-LA-OB have been used to clear the established biofilm communities.The silver-zwitterion nanocomposite achieved better penetration through bacterial biofilms and kill the bacteria embedded in biofilms,but also decrease the cytotoxity to mammalian cells.However,the cell compatibility of nanoparticles was not up to the requirement in vivo application.Think about it in a different way,based on the excellent bactericidal performance of silver nanoparticles,modification surface was designed to prevent bacterial adhesion and inhibit the formation of biofilm that can stop the infection spreading.In this chapter,we proposed to functional silver nanoparticles with biocompatible cationic polymer(PEI-Au NRs)and enzyme response degradable multilayer membranes(HA/PEI-AgNPs)were designed based on positively charged silver nanoparticles and hyaluronic acid(HA)by using layer-by-layer assembly method.Owing to the high biocompatibility and negative charge of HA were incorporated into films,we expect the(HA/PEI-AgNPs)multilayer showed low toxicity to mammalian cells.The negative charge of HA in the outermost layer can also effectively reduce bacterial adhesion.In addition,the obtained multilayer film can gradually degrade in hyaluronidase solutions and triggering the release of cationic silver nanoparticles which were overexpress in bacterial infection microenvironment.Furthermore,the(HA/PEI-AgNPs)multilayer films degradation of enzyme-triggered can removes the surface-attached bacteria and showed “self-cleaning” performance.Raman spectrometer and scanning electron microscopy images of the assemblies showed the gradual growth behavior with the number of deposited bilayers.Moreover,the enzymatic spalling and releasing behavior in enzyme and bacterial solution which exhibited effective on-demand self-defense release properties of the multilayer films.Meanwhile,the modified Lb L multilayer films showed good antifouling activities and antibacterial ability against model bacteria as measured by standard plate counting assay and live/dead staining method.Notably,the obtained antibacterial films showed superior antifouling properties against the model proteins.In conclusion,this work provides new strategies that may effectively inhibit the occurrence of biofilm infection-related diseases.