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

Abstract

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.