Photoactivated Release of Nitric Oxide and Antimicrobial Peptide Derivatives for Synergistic Therapy of Bacterial Skin Abscesses

It is of paramount importance to develop novel approaches for combating bacterial resistance and the integration of different antibacterial mechanisms is essential to achieve synergistic bactericidal efficiency while reducing the associated side effects. Herein, amphiphilic antimicrobial copolymers derived from poly‐l‐lysine (PLL), black phosphorus quantum dots (BPQDs) as near‐infrared (NIR) sensitizer, and S‐nitrosocysteamine (SNO) as nitric oxide (NO) donor, are assembled into PELI@BPQD‐SNO nanoparticles through electrostatic interactions. Amphiphilic copolymers with isopentanyl grafts on PLL at a ratio of 50% achieve an optimal balance between antibacterial activity and hemolysis rate. Photothermal effect of BPQDs leads to NIR‐responsive release of NO and the combination with amphiphilic copolymers mutually enhances long‐term inhibition of bacterial growth. In an S. aureus‐infected subcutaneous abscess model, the bactericidal rate of PELI@BPQD‐SNO/NIR treatment reaches nearly 99.6%, which is significantly higher than those without NO release (38%) or amphiphilic copolymers (24%) or NIR irradiation (17%). PELI@BPQD‐SNO/NIR treatment shows full recovery of infected wounds, efficient retardation of inflammatory cells, and reconstruction of blood vessels similar to those of healthy skin. Therefore, the electrostatic assembly demonstrates a promising strategy to deliver charged therapeutic agents and the photoactivated release of NO and amphiphilic copolymers achieves synergistic antibacterial efficacy without using any antibiotics. Bacterial resistance to antibiotics is becoming a major and even fatal global human health issue. Antimicrobial peptides and reactive oxide species are effective nonantibiotic antimicrobial agents but usually need relatively large doses. To address the challenges, antibacterial nanoparticles are developed with integration of near infrared‐triggered photothermal therapy and concurrent release of nitric oxide and cationic amphiphilic polymers.