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

Abstract The intervention of endogenous H 2 O 2 via nanozymes provides a potential antitumor‐specific therapy; however, the role of the nanozyme structure in relation to the selective decomposition of H 2 O 2 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─N 2 Cl 2 ─C SAzyme) is reported, which is prepared through precise Fe─Cl coordination based on the construction of a characteristic Fe‐containing molecule. Fe─N 2 Cl 2 ─C exhibits efficient catalytic H 2 O 2 decomposition (2.19 × 10 6 m m −1 s −1 ), which is the highest among reported SAzymes. More importantly, it is found that H 2 O 2 selectively decomposed into •OH on the Fe─N 2 Cl 2 ─C surface, which is attributable to the d orbitals of the Fe active center matching the O‐2 p electrons of the adsorbed hydroxide (*OH) intermediate. Fe─N 2 Cl 2 ─C is strongly cytotoxic toward a variety of cancer‐cell lines in vitro but not to normal cells. Furthermore, Fe─N 2 Cl 2 ─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 H 2 O 2 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.