Antimicrobial Peptide-Loaded Gelatinase-Responsive Photothermal Nanogel for the Treatment of Staphylococcus aureus-Infected Wounds

As the most common pathogen of community and nosocomial infection, the resistance of Staphylococcus aureus (S. aureus) to traditional antibiotics is still increasing with years. Although the potent antibacterial activity of antimicrobial peptides (AMPs) has been widely confirmed, the unpredictable cytotoxicity remains the biggest obstacle to their clinical application. The development of a targeted drug delivery system for S. aureus is a practical strategy to ameliorate the inherent limitations of AMPs. In this work, we constructed an AMP release nanogel (cypate-GNPs@Cy3-AMP, CGCA) of S. aureus infection microenvironment using gelatinase nanoparticles (GNPs) for toxicity control and bacterial clearance. Gelatinase present in the infected site degrades GNPs, thus releasing Cy3-AMP in situ to destroy bacterial cells. Cypate modified on the surface of GNPs supports CGCA to generate localized heat under near-infrared (NIR) laser irradiation, which together with AMPs could cause irreversible physical damage to bacteria. In addition, the encapsulation from GNPs not only effectively limited the toxicity of AMPs but also significantly promoted cell proliferation and migration in vitro. In the mouse infection model, CGCA also exhibited excellent effects of bacterial clearance and wound healing, providing a potential direction for the correct use of AMPs.