Controlled Modification of Axial Coordination of Single-Atom Nanozymes for Biomedical Applications

Natural enzymes and traditional artificial enzyme mimics are limited in biomedical applications by high costs, instability, or insufficient structural complexity. Nanozymes address some issues but lack sophistication and clear structure-activity relationships. Single-atom catalysts (SACs) bridge natural enzymes and nanozymes, while single-atom nanozymes (SAzymes) with tailored axial coordination further enhance enzyme-like activities by modulating electronic structures via axial ligands. Here we summarize advances in axially coordinated SAzymes for biomedicine: this review categorizes synthetic strategies (dominated by high-temperature pyrolysis, supplemented by solvothermal and supramolecular assembly methods); elaborates on axial coordination designs (nitrogen-group, chalcogen-containing, halogen-containing, and other ligands); and highlights applications in colorimetric biosensing, tumor therapy, and antimicrobial therapy. Finally, we outline challenges and perspectives on controllable synthesis, mechanism elucidation, biosafety to guide rational design and clinical translation of axially coordinated SAzymes.