While carbon dots (CDs)-based single-atom nanozymes hold great promise, their customized design guided by precise structure-activity relationships remains challenging. Herein, we report the rational synthesis of zinc single-atom CDs (Zn-CDs) featuring isolated Zn catalytic centers firmly anchored by oxygen-rich surface functional groups. Benefiting from the atomic Zn-O 4 sites for electron transfer, the Zn-CDs exhibit exceptional antioxidant performance. Specifically, they achieve a remarkable superoxide anion (·O 2 - ) scavenging efficiency of over 96% at a low dosage of 30 μg/mL, accompanied by ·OH elimination capacity and superior thermal and pH stability that outperform natural enzymes. Biologically, these Zn-CDs demonstrate excellent biocompatibility and efficiently alleviate intracellular oxidative stress, thereby inducing and promoting the osteogenic differentiation of stem cells. Mechanistically, this osteoinductive process is driven by the activation of the classical Wnt/β-catenin signaling pathway and the upregulation of pivotal osteogenic markers including RUNX2 , SP7 , COL1A1 , and BGLAP . Supported by density functional theory (DFT) calculations, this work elucidates the atomic-level charge transfer mechanism of Zn-CDs, presenting a paradigm for customizing highly efficient and safe single-atom nanozymes for regenerative medicine. • Rational design of Zn single-atom NPs for bio-applications. • Surface Zn-O 4 sites drive superior SOD-like activity. • Zn-CDs regulate intracellular ROS at the bio-interface. • Inherited osteogenic capability promotes bone regeneration. • A robust strategy for multifunctional nanozyme engineering.
Li et al. (Sun,) studied this question.