Ciprofloxacin conjugated gold nanorods with pH induced surface charge transformable activities to combat drug resistant bacteria and their biofilms

Abstract

The ever-growing threat of drug-resistant pathogens and their biofilms based persistent, chronic infections has created an urgent call for new strategies to deal with multidrug resistant bacteria (MDR). Near-infrared (NIR) laser-induced photothermal treatment (PTT) of gold nanorods (AuNRs) disinfects microbes by local heating with low possibility to develop resistant. However, PTT disinfection strategy of AuNRs alone shows less efficiency in killing multidrug resistant strains (i.e. Methicillin-resistant Staphylococcus aureus, MRSA) and their matured biofilms. Herein, a novel synergistic chemo-photothermal integrated antimicrobial platform (P(Cip-b-CB)-AuNRs) was fabricated which show enhanced killing efficiency against MRSA in both planktonic and biofilm phenotypes. Polymethacrylate copolymers with pendant ciprofloxacin (Cip) and the carboxyl betaine groups (P(Cip-b-CB)) were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. P(Cip-b-CB) was decorated onto AuNRs via gold-thiol bond which resulted in AuNRs with acidic-induced surface charge-switchable activities and lipase triggered Cip release properties (P(Cip-b-CB)-AuNRs). The lower pH value and overexpress of lipase are characteristics for microenvironment of microbial infections and their biofilms, which ensure the targeting on, penetration into and on-demand release of Cip from the nanocomposites in bacterial infection sites and their biofilms. The bacterial cell membrane was disrupt by photothermal therapy which could improve its permeability and sensitivity to antibiotics, meanwhile lipase-triggered release of Cip ensures a high concentration of antibiotics at the site of bacterial infection. Besides their NIR induced PTT disinfection activities, the increased local temperature generated by NIR light irradiation accelerated Cip release which further enhanced the antibacterial efficiency, leading to synergistic antibacterial activities of chemo-photothermal therapy. Taken together, the designed synergistic chemo-photothermal integrated antimicrobial platform is a promising antibacterial agent for fighting MDR bacterial infections and their biofilms.

Keywords: Biofilm; Combined chemo-photothermal therapy; Drug-resistant bacteria; Gold nanorods; pH-responsive.