Augmenting the catalytic activity of ADzymes: strategic engineering from atomic structure design to macro-environmental interaction for enhanced biomedical efficacy

Nanozymes with atomically dispersed metal sites (ADzymes), characterized by well-defined active centers, high catalytic efficiency, and tunable catalytic properties, have expanded the horizons for developing bio-inspired solutions to address critical challenges in healthcare domains. Herein, this article systematically reviews the synthesis and characterization methods, and classification system of ADzymes, and summarizes the strategies to enhance their catalytic activity ranging from micro- to macro-scales. Key strategies discussed include the biomimetic design of metal active centers, modulation of coordination environments, support interface engineering, and external-field-responsive dynamic activation. Furthermore, the potential applications of ADzymes in ROS-mediated biomedical therapies are highlighted. Based on the systematic deconstruction of the structure-activity relationship, this review provides a theoretical foundation for the rational design of high-performance artificial enzymes. Finally, the current bottlenecks and future perspectives regarding the regulation of ADzymes for clinical translation are discussed, providing insights into their evolution from empirical screening to intelligent design.