Molybdenum disulfide nanosheets based non-oxygen-dependent and heat-initiated free radical nanogenerator with antimicrobial peptides for antimicrobial, biofilm ablation and wound healing

Chronic refractory wounds caused by multidrug-resistant (MDR) bacterial and biofilm infections are a substantial threat to human health, which presents a persistent challenge in managing clinical wound care. We here synthesized a composite nanosheet AIPH/AMP/MoS2, which can potentially be used for combined therapy because of the photothermal effect induced by MoS2, its ability to deliver antimicrobial peptides, and its ability to generate alkyl free radicals independent of oxygen. The synthesized nanosheets exhibited 61 % near-infrared (NIR) photothermal conversion efficiency, marked photothermal stability and free radical generating ability. The minimal inhibitory concentrations (MICs) of the composite nanosheets against MDR Escherichia coli (MDR E. coli) and MDR Staphylococcus aureus (MDR S. aureus) were approximately 38 μg/mL and 30 μg/mL, respectively. The composite nanosheets (150 μg/mL) effectively ablated >85 % of the bacterial biofilm under 808-nm NIR irradiation for 6 min. In the wound model experiment, approximately 90 % of the wound healed after the 4-day treatment with the composite nanosheets. The hemolysis experiment, mouse embryonic fibroblast (MEFs) cytotoxicity experiment, and mouse wound healing experiment all unveiled the excellent biocompatibility of the composite nanosheets. According to the transcriptome analysis, the composite nanosheets primarily exerted a synergistic therapeutic effect by disrupting the cellular membrane function of S. aureus and inhibiting quorum sensing mediated by the two-component system. Thus, the synthesized composite nanosheets exhibit remarkable antibacterial and biofilm ablation properties and therefore can be used to improve wound healing in chronic biofilm infections.