Geometric Tuning of Single‐Atom FeN ₄ Sites via Edge‐Generation Enhances Multi‐Enzymatic Properties

Abstract Single‐atom nanozymes (SAzymes) are considered promising alternatives to natural enzymes. The catalytic performance of SAzymes featuring homogeneous, well‐defined active structures can be enhanced through elucidating structure‐activity relationship and tailoring physicochemical properties. However, manipulating enzymatic properties through structural variation is an underdeveloped approach. Herein, the synthesis of edge‐rich Fe single‐atom nanozymes (FeNC‐edge) via an H ₂ O ₂ ‐mediated edge generation is reported. By controlling the number of edge sites, the peroxidase (POD)‐ and oxidase (OXD)‐like performance is significantly enhanced. The activity enhancement results from the presence of abundant edges, which provide new anchoring sites to mononuclear Fe. Experimental results combined with density functional theory (DFT) calculations reveal that FeN ₄ moieties in the edge sites display high electron density of Fe atoms and open N atoms. Finally, it is demonstrated that FeNC‐edge nanozyme effectively inhibits tumor growth both in vitro and in vivo, suggesting that edge‐tailoring is an efficient strategy for developing artificial enzymes as novel catalytic therapeutics.