Coordination-Driven Self-Assembly Strategy-Activated Cu Single-Atom Nanozymes for Catalytic Tumor-Specific Therapy
Jie Zhou, Deting Xu, Gan Tian, Qian He, Xiao Zhang, Jing Liao, Linqiang Mei, Lei Chen, Lizeng Gao, Lina Zhao, Guo‐Ping Yang, Wenyan Yin, Guangjun Nie, Yuliang Zhao
Abstract
How to optimize the enzyme-like catalytic activity of nanozymes to improve their applicability has become a great challenge. Herein, we present an l -cysteine ( l -Cys) coordination-driven self-assembly strategy to activate polyvinylpyrrolidone (PVP)-modified Cu single-atom nanozymes MoO x -Cu-Cys (denoted as MCCP SAzymes) aiming at catalytic tumor-specific therapy. The Cu single atom content of MCCP can be rationally modulated to 10.10 wt %, which activates the catalase (CAT)-like activity of MoO x nanoparticles to catalyze the decomposition of H 2 O 2 in acidic microenvironments to increase O 2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO 2 nanozymes and exhibits 14.3-fold higher affinity than natural catalase, as demonstrated by steady-state kinetics. We verify that the well-defined l -Cys-Cu···O active sites optimize CAT-like activity to match the active sites of natural catalase through an l -Cys bridge-accelerated electron transfer from Cys-Cu to MoO x disclosed by density functional theory calculations. Simultaneously, the high loading Cu single atoms in MCCP also enable generation of •OH via a Fenton-like reaction. Moreover, under X-ray irradiation, MCCP converts O 2 to 1 O 2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.