An Ultrasmall Fe3O4‐Decorated Polydopamine Hybrid Nanozyme Enables Continuous Conversion of Oxygen into Toxic Hydroxyl Radical via GSH‐Depleted Cascade Redox Reactions for Intensive Wound Disinfection

Abstract Nanozyme‐based chemodynamic therapy (CDT) for fighting bacterial infections faces several major obstacles including low hydrogen peroxide (H 2 O 2 ) level, over‐expressed glutathione (GSH) in infected sites, and inevitable damage to healthy tissue with abundant nonlocalized nanozymes. Herein, a smart ultrasmall Fe 3 O 4 ‐decorated polydopamine (PDA/Fe 3 O 4 ) hybrid nanozyme is demonstrated that continuously converts oxygen into highly toxic hydroxyl radical (•OH) via GSH‐depleted cascade redox reactions for CDT‐mediated bacterial elimination and intensive wound disinfection. In this system, photonic hyperthermia of PDA/Fe 3 O 4 nanozymes can not only directly damage bacteria, but also improve the horseradish peroxidase‐like activity of Fe 3 O 4 decorated for CDT. Surprisingly, through photothermal‐enhanced cascade catalytic reactions, PDA/Fe 3 O 4 nanozymes can consume endogenous GSH for disrupting cellular redox homeostasis and simultaneously provide abundant H 2 O 2 for improving •OH generation, ultimately enhancing the antibacterial performance of CDT. Such PDA/Fe 3 O 4 can bind with bacterial cells, and reveals excellent antibacterial property against both Staphylococcus aureus and Escherichia coli . Most interestingly, PDA/Fe 3 O 4 nanozymes can be strongly retained in infected sites by an external magnet for localized long‐term in vivo CDT and show minimal toxicity to healthy tissues and organs. This work presents an effective strategy to magnetically retain the therapeutic nanozymes in infected sites for highly efficient CDT with good biosafety.