A Bioinspired Cascade SAzyme: Ti³⁺-Mediated Stabilization of Cu Single-Atoms on TiO_2-x for Efficient ROS Scavenging

While antioxidant therapies targeting reactive oxygen species (ROS) overproduction and inflammation hold clinical promise, developing effective and durable nanozymes remains challenging. To address this, a highly efficient copper single-atom nanozyme (Cu_SA/TiO_2-x) is engineered, exhibiting robust superoxide dismutase-like activity and significant glutathione peroxidase-like functionality. This dual-action design enabled efficient ROS scavenging and consequent suppression of inflammation in lipopolysaccharide-stimulated macrophages. Crucially, the presence of Ti³⁺ in TiO_2-x support enhances the stabilization of Cu_SA/TiO_2-x by promoting the reduction of Cu²⁺ ions to Cu⁺ ions, thereby facilitating robust metal immobilization. Moreover, SAzyme catalytic activity is systematically modulated through metal selection and loading control, achieving effective tuning of enzyme-like activity across different metal-SAzyme systems. This innovative synthesis and application of Cu_SA/TiO_2-x offers a promising strategy for the controlled synthesis of TiO₂-based SAzymes and advances their potential in medical applications.