Selenide‐Driven Reactive Oxygen Species Activation and Fe(II) Regeneration for Enhanced Nanocatalytic Antibacterial Therapeutics

Abstract Fenton‐based nanocatalytic therapy has attracted widespread attention for its high efficiency and safety. Nevertheless, Fe 2+ regeneration, as the rate‐limiting step of Fenton reaction, hinders the ROS‐induced oxidative killing. Herein, a Fe 2+ auto‐regeneration strategy is exemplified by 2D FeSe 2 nanosheets to break the rate limitation of Fenton reaction and subsequently enhances the antibacterial oxidative damage via dual ROS generation pathways. To be specific, the Se species accelerate the Fe 3+ reduction to maintain high ·OH productivity of Fe 2+ ‐mediated Fenton reaction, which is accompanied by the production of H 2 Se in the presence of H + . The H 2 Se further converts O 2 into O 2 ·− and synergistically breaks the oxidative threshold of bacteria, leading to irreversible bacterial death with glutathione depletion, lipid peroxidation, and membrane destruction. In summary, the FeSe 2 ‐mediated Fe 2+ auto‐regeneration and ROS self‐production pathways largely elevate its oxidative killing capability, providing a potential ROS enhancement strategy for broad‐spectrum nonantibiotic bacterial disinfection.