Atomically Engineered Chlorine Coordination of Iron in Active Centers for Selectively Catalytic H₂O₂ Decomposition Toward Efficient Antitumor‐Specific Therapy

The intervention of endogenous H₂O₂ via nanozymes provides a potential antitumor-specific therapy; however, the role of the nanozyme structure in relation to the selective decomposition of H₂O₂ to hydroxyl radicals (•OH) is yet to be fully understood, which limits the development of this therapeutic approaches. Herein, an iron single-atom nanozyme (Fe─N₂Cl₂─C SAzyme) is reported, which is prepared through precise Fe─Cl coordination based on the construction of a characteristic Fe-containing molecule. Fe─N₂Cl₂─C exhibits efficient catalytic H₂O₂ decomposition (2.19 × 10⁶ mm^-1 s^-1), which is the highest among reported SAzymes. More importantly, it is found that H₂O₂ selectively decomposed into •OH on the Fe─N₂Cl₂─C surface, which is attributable to the d orbitals of the Fe active center matching the O-2p electrons of the adsorbed hydroxide (*OH) intermediate. Fe─N₂Cl₂─C is strongly cytotoxic toward a variety of cancer-cell lines in vitro but not to normal cells. Furthermore, Fe─N₂Cl₂─C shows an outstanding specific therapeutic effect in vivo; it efficiently destroys solid malignant tumors without injuring normal tissue. Altogether, these findings highlight the selective catalytic decomposition of H₂O₂ to •OH, which is achieved by engineering the active center on the atomic level, thereby providing an avenue for the development of specific nanomedicines with efficient antitumor activities.