Combined photothermal and antibiotic therapy for bacterial infection via acidity-sensitive nanocarriers with enhanced antimicrobial performance

Abstract Integration of two distinctive bactericides into one platform is a promising strategy to enhance the efficiency of antimicrobial agents. We reported an efficient chemo-photothermal therapeutic platform based on polydopamine (PDA)-coated gold nanorods (PDA@GNRs). Then the PDA@GNRs were further grafted with glycol chitosan (GCS-PDA@GNRs), which became positively charged in the low pH environment of bacterial infection sites, allowing them to accumulate/retain at local infection site as revealed by thermal imaging. The PDA coating acquires high loading efficiency of daptomycin (DAP) and pH-sensitive DAP release ability. The acidity-activated release of DAP could effectively damage the bacterial membrane, causing permeability increase and heat resistance reduction of the cell membrane, leading to large improvement on bactericidal efficiency of photothermal therapy. On the other hand, the hyperthermia could trigger more DAP release, resulting in further improvement on bactericidal efficiency of chemotherapy. Moreover, combined chemo-hyperthermia therapy of DAP loaded GCS-PDA-PDA@GNRs (DAP-GCS-PDA@GNRs) could thoroughly ablate abscess and accelerate wound healing via a synergistic antibacterial effect as well as exhibit negligible biotoxicity in vitro and in vivo. Therefore, our study demonstrates that combining antimicrobial therapy along with a stimulus-responsive moiety represents a feasible way to treat the bacterial-induced skin infection.