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

ABSTRACT

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.