NIR/pH-responsive arginine-ε-polylysine/black phosphorus nanocomposites for synergistic therapy of bacterial infections

The escalating global burden of drug-resistant bacterial infections demands urgent innovation in highly effective, non-invasive antimicrobial strategies. Herein, we developed a multimodal near infrared (NIR) light-responsive bactericidal nanoplatform (BP@EPL-LA) with surface charge adaptability by loading black phosphorus nanosheets with L-Arg-grafted ε-poly(L-lysine) for targeted combinatorial therapy of subcutaneous abscesses. Under physiological conditions, BP@EPL-LA remained a neutral surface charge and demonstrated excellent biosafety both <i>in vitro</i> and <i>in vivo</i>. Upon encountering the acidic infectious environment, BP@EPL-LA rapidly switched to a positive surface charge, promoting deep biofilm penetration and strong electrostatic adhesion to negatively charged bacterial membranes. When irradiated by 660 nm laser, BP@EPL-LA mediated antibacterial photodynamic therapy (aPDT), generating reactive oxygen species (ROS) that oxidized arginine residues to enable controlled nitric oxide (NO) release. BP@EPL-LA effectively dispersed bacterial biofilms and demonstrated broad-spectrum antibacterial activity through the synergistic combination of ROS, NO, and EPL. Moreover, BP@EPL-LA showed remarkable therapeutic outcomes in a mouse model of subcutaneous Methicillin-resistant <i>Staphylococcus aureus</i> abscesses, simultaneously eradicating bacterial infection, reducing inflammation, and promoting tissue healing <i>via</i> enhanced vascularization and collagen deposition. Therefore, BP@EPL-LA overcomes antibiotic resistance barriers and presents a promising therapeutic strategy for effective subcutaneous abscess treatment by integrating NO-potentiated aPDT with EPL's bactericidal action.