Engineering Atomically Dispersed Cu–N1S2 Sites via Chemical Vapor Deposition to Boost Enzyme‐Like Activity for Efficient Tumor Therapy

Abstract Single‐atom nanozymes (SAzymes), with well‐defined and uniform atomic structures, are an emerging type of natural enzyme mimics. Currently, it is important but challenging to rationally design high‐performance SAzymes and deeply reveal the interaction mechanism between SAzymes and substrate molecules. Herein, this work reports the controllable fabrication of a unique Cu−N 1 S 2 ‐centred SAzyme (Cu‐N/S‐C) via a chemical vapor deposition‐based sulfur‐engineering strategy. Benefiting from the optimized geometric and electronic structures of single‐atom sites, Cu‐N/S‐C SAzyme shows boosted enzyme‐like activity, especially in catalase‐like activity, with a 13.8‐fold increase in the affinity to hydrogen peroxide (H 2 O 2 ) substrate and a 65.2‐fold increase in the catalytic efficiency when compared to Cu‐N‐C SAzyme with Cu−N 3 sites. Further theoretical studies reveal that the increased electron density around single‐atom Cu is achieved through electron redistribution, and the efficient charge transfer between Cu‐N/S‐C and H 2 O 2 is demonstrated to be more beneficial for the adsorption and activation of H 2 O 2 . The as‐designed Cu‐N/S‐C SAzyme possesses an excellent antitumor effect through the synergy of catalytic therapy and oxygen‐dependent phototherapy. This study provides a strategy for the rational design of SAzymes, and the proposed electron redistribution and charge transfer mechanism will help to understand the coordination environment effect of single‐atom metal sites on H 2 O 2 ‐mediated enzyme‐like catalytic processes.