Iron Single Atom Nanozyme-Mediated GPX4 Inhibitor Delivery for Self-Enhanced Ferroptosis

OH to trigger LPO and glutathione oxidase-like activity that depletes intracellular GSH to inactivate GPX4. Meanwhile, the loaded Fin56 exerts synergistic GPX4 inhibition, amplifying the ROS cascade. In vitro and in vivo assays confirm that Fe-SAN@F induces irreversible tumor ferroptosis via the combined effects of LPO accumulation, GSH depletion, and GPX4 inactivation, effectively suppressing tumor proliferation. This work establishes a novel SAN-based catalytic therapy paradigm for remodeling the TME and boosting ferroptosis, providing a rational design strategy for next-generation precision antitumor nanozymes.