Preparation And Antibacterial Appliactions Of Gold Nanorods With PH Induced Surface Charge Switchable Properties

Bacterial infectious diseases have aroused sustained extensive concernsin as one of the most significant public healthcare problems around the world in recent decades.The usage of antibiotics regarded as the most efficient method to cure bacteria infections.But the frequent and excessive use of antibiotics has caused the increasing rate of bacterial resistance,which not only reduces the effectiveness of clinical antibacterial agents but also lead to the high risk of death.Thus,the demands of developing new and efficient antibacterial strategies without reduce resistance to treat diseases caused by bacteria.Particularly,near-infrared(NIR)light-mediated photothermal therapy(PTT)has many special advantages including effective treatment,penetrate tissues deeply while causing minimal noninvasiveness to surrounding areas,has received considerable attention in recent decades.Unlike antibiotics,PTT can rapidly kill bacterial cells by rising local temperature which provide new opportunities for the biological antibacterial.In this paper,we took advantage of the excellent photothermal of gold nanorods(AuNRs)upon NIR laser irradiation,two kinds of goldbased photothermal reagent were designed to decrease the cytotoxity to mammalian cells while increase their antibacterial and antibiofilm efficiency.The concrete work was as follows:(1)As an attempt to increase the biocompatibility and their antibacterial activities against both planktonic phases and biofilm embedded bacteria,polymethacrylate with pendant carboxyl betaine groups were decorated on AuNRs(PCB-AuNRs)by gold-thiol bond which resulted AuNRs with pH induced surface charge transformable activities.The zwitterion modified AuNRs were found pH-responsive transition from negative charge to positive charge,which confer the AuNRs change in functionality from a biocompatible zwitterionic nanocomposites in healthy tissues(pH?7.4)to an enhanced antimicrobial cationic nanocomposites at acidic bacterial infection sites(pH?5.5).It is demonstrated that PCB-AuNRs significantly enhance the interaction with bacteria and presented good photothermal antimicrobial activity efficiency against Gram-negative bacteria(E.coli)and Gram-positive bacteria(S.aureus)as a result of their pH responsive surface charge transition activities.Moreover,PCB-AuNRs demonstrated deeper penetration into matured biofilms and better biofilm elimination activities.The results indicate the designed zwitterion coated AuNRs as a promising candidate antibacterial agent for fighting bacterial infection.(2)It is demonstrated that PCB-AuNRs presented deeper penetration into matured biofilms and better biofilm elimination activities,but also improved photothermal disinfection efficiency against drug-resistant strains.However,the killing efficiency of drug-resistant bacteria by single photothermal effect was not up to the requirement.Therefore,we integration the infrared-activated photothermal of AuNRs with antibiotic bactericides(taking ciprofloxacin as an example)into one platform synergistic therapy to address multidrug resistance bacterial infection by covalent bond grafted the antibiotic ciprofloxacin and zwitterion carboxylic acid betaine onto the gold nanorods using RAFT reaction.The specific structure of carboxylate betaine has one carboxylate anion and quaternary amine cationic group at the microscopic range,which could form hydration layer via electrostatic interactions to resist nonspecific protein adsorptionthe and endows gold nanoroads with water-soluble and targeted functions.On the other hand,the protonation of carboxyl groups at an acidic microenvironment results in positive charged AuNRs which enhance the interaction of nanoparticles with bacteria,causing the long retention of the bactericides in the infectious environment.The lipaseactivated release of Cip could effectively damage the structure of bacterial membrane,which were overexpressed in the infection site.Leading to large improvement on bactericidal efficiency of photothermal therapy and excellent cell compatibility by a series of experiments and research.Drug release test showed that the hyperthermia could trigger more antibiotics release,resulting in further improvement on bactericidal efficiency of photothermal therapy and play a synergistic bactericidal effect.