Proximal-distal coordination engineering of iron single-atom nanozyme for synergistic multi-enzymatic-photothermal control of antibiotic-resistant bacteria

The escalating threat of antibiotic-resistant bacteria in environmental and clinical settings poses a serious risk to public health and ecosystem safety. Conventional nanozyme designs often struggle to balance catalytic activity and substrate adsorption, limiting their efficacy in mitigating such hazards. Herein, we report a proximal-distal coordination engineering strategy that achieves synergistic enhancement through first-sphere symmetry breaking (S doping) and second-sphere electronic regulation (-OH incorporation). This dual modification elevates peroxidase-like activity to 5.5 times that of pristine Fe-NC (5.00 mg^-1), alongside excellent catalase-like, glutathione oxidase-like activities, and photothermal performance. Density functional theory reveals a shifted Fe d-band center (from -1.97 eV to -0.53 eV), enhancing substrate adsorption, while -OH reduces Fe-S bond localization, facilitating charge transfer. The engineered nanozyme eliminates > 99.9% of S. aureus and E. coli under near-infrared irradiation with trace H₂O₂, disrupting bacterial tricarboxylic acid cycle, ATP synthesis, and central carbon metabolism. In a mouse wound infection model, it accelerates wound closure, promotes collagen deposition, and reduces IL-6 and TNF-α, with good biocompatibility. This work provides a sustainable, non-antibiotic antimicrobial platform for managing bacterial contamination and mitigating the risk of resistance propagation in environmental matrices.