Atomically Engineered Chlorine Coordination of Iron in Active Centers for Selectively Catalytic HO Decomposition Toward Efficient Antitumor-Specific Therapy.

The intervention of endogenous HO via nanozymes provides a potential antitumor-specific therapy; however, the role of the nanozyme structure in relation to the selective decomposition of HO 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─NCl─C SAzyme) is reported, which is prepared through precise Fe─Cl coordination based on the construction of a characteristic Fe-containing molecule. Fe─NCl─C exhibits efficient catalytic HO decomposition (2.19 × 10 mm s), which is the highest among reported SAzymes. More importantly, it is found that HO selectively decomposed into •OH on the Fe─NCl─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─NCl─C is strongly cytotoxic toward a variety of cancer-cell lines in vitro but not to normal cells. Furthermore, Fe─NCl─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 HO 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.