Single-atom nanozymes for antitumor catalytic therapy: structural engineering, catalytic mechanism, and advanced...

Single-atom nanozymes (SAzymes) have emerged as a transformative platform for antitumor catalytic therapy, uniquely combining the catalytic efficiency of natural enzymes with the structural robustness of conventional nanozymes. Their atomically dispersed metal centers achieve 100% atomic utilization, eliminate active-site interference, and enable coordination-level structural engineering, allowing precise control over electronic structure and catalytic selectivity. This review systematically examines the core advancements driving SAzyme development: (i) the rational design of metal centers and coordination environments, (ii) carrier engineering through single-support optimization and heterojunction construction; (iii) innovative catalytic mechanisms, including ROS regulation, and induction of novel cell death pathways; and (iv) advanced therapeutic strategies, such as tumor microenvironment (TME)-responsive activation, multimodal synergy, and targeted delivery. Despite progress, critical challenges remain such as unresolved dynamic mechanisms, the loading-dispersion paradox, and barriers to clinical translation. We emphasize that atomic-level precision in SAzyme design is revolutionizing antitumor therapy. In addition, we identify intelligent dynamic systems and clinically oriented manufacturing as two key directions, which will promote the transformation of SAzymes from laboratory innovations to practical clinical applications in oncology.