Self-Adaptive Nanozymes With Enhanced Multi-Enzyme Activities for Sequential Multimodal Therapy of Drug-Resistant Bacteria-Infected Wounds

The study presents a novel therapeutic approach for treating drug-resistant bacteria-infected wounds using a self-adaptive IrPtCu nanozyme embedded in a madecassoside-enriched hyaluronic acid hydrogel (HIPCM). This platform leverages the synergy of trimetallic components and pH-adaptive reactive oxygen species (ROS) regulation to exhibit multiple enzyme-like activities, enabling efficient ROS generation for antibacterial action and subsequent ROS scavenging to alleviate oxidative stress. In a methicillin-resistant Staphylococcus aureus (MRSA)-infected mouse model, HIPCM demonstrated strong antibacterial efficacy, promoted M2 macrophage polarization, angiogenesis, and accelerated wound healing. Preclinical studies in Bama mini-pigs confirmed improved collagen deposition, hair follicle regeneration, and functional restoration, highlighting the potential of integrating adaptive nanozymes with natural herbal medicines for effective treatment of drug-resistant wounds.