FeS ₂ @ZIF-67 Core–Shell Nanozymes for Cascade Catalysis to Eradicate Resistant Bacteria and Biofilms in Wound Therapy

Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Klebsiella pneumoniae are major pathogens in hospital-acquired skin and soft tissue infections, leading to delayed healing and increased mortality. To address multidrug resistance, we developed a core–shell FeS2@ZIF-67 nanozyme via an in situ self-assembly strategy. The zeolitic imidazolate framework-67 (ZIF-67) coating acts as a protective layer, suppressing oxidation and aggregation of the catalytically active but unstable FeS2 core whereas preserving its intrinsic peroxidase-like activity. Therefore, FeS2@ZIF-67 exhibits high catalytic stability and efficiency, converting H2O2 into highly cytotoxic hydroxyl radicals for potent antibacterial activity. In vitro, FeS2@ZIF-67 combined with H2O2 achieved strong bactericidal effects against MRSA and K. pneumoniae. Notably, the treatment also concentration-dependently disrupted the architecture of preformed MRSA biofilms. In the MRSA-infected full-thickness wound model, the synergistic treatment not only expedited wound closure but also restored inflammatory balance, promoted angiogenesis, and enhanced collagen deposition, thereby facilitating comprehensive tissue regeneration. Overall, FeS2@ZIF-67 integrates targeted antibacterial activity with favorable biosafety, offering a promising therapeutic platform for managing drug-resistant wound infections.