Self-Adaptive Single-Atom Catalyst Boosting Selective Ferroptosis in Tumor Cells

Ferroptosis, resulting from the catastrophic accumulation of lipid reactive oxygen species (ROS) and the inactivation of glutathione (GSH)-dependent peroxidase 4 (GPX4), has emerged as a form of regulated cell death for cancer therapy. Despite progress made with current ferroptosis inducers, efficient systems to trigger ferroptosis remain challenging, owing largely to their low activity, uncontrollable behavior, and even nonselective interactions. Here, we report a self-adaptive ferroptosis platform by engineering a DNA modulator onto the surface of single-atom nanozymes (SAzymes). The modulator could not only specifically intensify the ROS-generating activity but also endow the SAzymes with on-demand GSH-consuming ability in tumor cells, accelerating selective and safe ferroptosis. The self-adaptive antitumor response has been demonstrated in colon cancer and breast cancer, promoting the development of selective cancer therapy.