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 Fe3O4 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. A melamine‐mediated pyrolysis activation strategy is reported for the fabrication of a single‐atom iron nanozyme containing a five‐coordinated structure (FeN5). The catalytic efficiency of FeN5 with optimized coordination structure is significantly higher than traditional four‐coordinated single‐atom iron nanozyme (FeN4) and Fe3O4 nanozyme. As a proof of concept, FeN5 SAzyme achieves effective killing of tumor cells, and significantly prolongs the survival of mice in a 4T1‐tumor‐bearing mice model.