A Bioinspired Five-Coordinated Single-Atom Iron Nanozyme for Tumor Catalytic Therapy

Single-atom nanozymes (SAzymes) represent a new research frontier in the biomedical fields. The rational design and controllable synthesis of SAzymes with well-defined electronic and geometric structures are essential for maximizing their enzyme-like catalytic activity and therapeutic efficacy but remain challenging. Here, a melamine-mediated pyrolysis activation strategy is reported for the controllable fabrication of iron-based SAzyme containing five-coordinated structure (FeN₅ ), identified by transmission electron microscopy imaging and X-ray absorption fine structure analyses. The FeN₅ SAzyme exhibits superior peroxidase-like activity owing to the optimized coordination structure, and the corresponding catalytic efficiency of Fe-species in the FeN₅ SAzyme is 7.64 and 3.45 × 10⁵ times higher than those in traditional FeN₄ SAzyme and Fe₃ O₄ nanozyme, respectively, demonstrated by steady-state kinetic assay. In addition, the catalytic mechanism is jointly disclosed by experimental results and density functional theory studies. The as-synthesized FeN₅ SAzyme demonstrates significantly enhanced antitumor effect in vitro and in vivo due to the excellent peroxidase-like activity under tumor microenvironment.