Abstract
Background: Diabetic wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) are challenging to heal due to biofilm formation, which impairs conventional antibiotics with limited penetration and severe side effects. Near-infrared (NIR)-driven nanomotors with autonomous motion and photothermal effects show promise for antibacterial therapy but often lack targeted specificity. Lysostaphin (Ly), an enzyme targeting bacterial cell walls, offers excellent potential against drug-resistant MRSA. Methods: A novel NIR-driven CSIL nanomotor has fabricated by co-loading indocyanine green (ICG) and lysostaphin onto spinous yolk-shell structured C/SiO(2)@C nanoparticles. The autonomous motion, biofilm penetration, and antibacterial efficacy of CSIL nanomotors are evaluated in vitro, while their biofilm eradication and wound healing performance are assessed in an MRSA-infected diabetic mouse model using a cascade photodynamic therapy (CPDT) strategy. Results: CSIL nanomotors exhibit photothermal and photodynamic properties with MRSA-targeting specificity. They can effectively eradicate MRSA biofilms both in vitro and in vivo, suppress virulence and biofilm-related genes, thus promoting diabetic wound healing by shaping a microenvironment dominated by M2 macrophages. The CPDT strategy is able to avoid excessive ROS production and thermal damage, enabling safe and effective therapy. Conclusion: CSIL nanomotors, with integrated photothermal, photodynamic, and MRSA-targeting properties, represent a novel, efficient and targeted approach to antibacterial therapy in diabetic wounds, offering significant advantages over conventional antibiotics.