Iron/Cobalt Dual-Atom Catalyst Orchestrate Photothermal-Chemodynamic Immunotherapy Against MRSA: Multi-Omics Dissection in Murine and Porcine Models.

Abstract

Translating pathogen-specific molecular insights into effective treatments remains a significant challenge, particularly for drug-resistant wound infections. In this study, we develop a nitrogen-doped iron/cobalt dual-atom catalyst (FeCo-N-DAC) with high metal loading (Fe > 5.4%, Co > 4.8%) as a multifunctional platform that integrates nanozyme-mimicking catalytic activity and photothermal therapy. FeCo-N-DAC mimics multiple natural enzymes to generate reactive oxygen species, disrupt bacterial biofilms, and eradicate methicillin-resistant Staphylococcus aureus (MRSA) in both murine and porcine models of subcutaneous abscesses and infectious wounds, respectively. Upon near-infrared (NIR-II) irradiation, the material exhibits deep-seated tissue penetration and synergistic catalytic-photothermal effects, enabling complete biofilm clearance in otherwise recalcitrant infections. Multi-omics analyses, including transcriptomics and proteomics, reveal that FeCo-N-DAC modulates immune responses and promotes tissue regeneration by reprogramming inflammation- and fibrosis-related pathways. This study highlights the therapeutic potential of dual-atom nanozymes for precision anti-infective therapy and underscores their translational relevance in treating complex, biofilm-associated infections.