TY - JOUR
T1 - Coordination-Driven Self-Assembly Strategy-Activated Cu Single-Atom Nanozymes for Catalytic Tumor-Specific Therapy
AU - Zhou, Jie
AU - Xu, Deting
AU - Tian, Gan
AU - He, Qian
AU - Zhang, Xiao
AU - Liao, Jing
AU - Mei, Linqiang
AU - Chen, Lei
AU - Gao, Lizeng
AU - Zhao, Lina
AU - Yang, Guoping
AU - Yin, Wenyan
AU - Nie, Guangjun
AU - Zhao, Yuliang
N1 - Funding Information:
This work was supported by the National Basic Research Programs of China (2021YFA1200904), National Natural Science Foundation of China (22175182, U1932112, 81971747), Beijing Natural Science Foundation (2202064), Sheng Yuan Cooperation (2021SYHZ0048), and Chongqing Natural Science Foundation (cstc2020jcyj-msxmX0061). We also appreciate the support from beamlines of 1W1B and 4W1B at the Beijing Synchrotron Radiation Facility (BSRF).
Publisher Copyright:
© 2023 American Chemical Society.
PY - 2022
Y1 - 2022
N2 - 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 MoOx-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 MoOx nanoparticles to catalyze the decomposition of H2O2 in acidic microenvironments to increase O2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO2 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 MoOx 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 O2 to 1O2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.
AB - 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 MoOx-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 MoOx nanoparticles to catalyze the decomposition of H2O2 in acidic microenvironments to increase O2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO2 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 MoOx 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 O2 to 1O2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.
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U2 - 10.1021/jacs.2c13597
DO - 10.1021/jacs.2c13597
M3 - Article
C2 - 36744911
AN - SCOPUS:85147991287
SN - 0002-7863
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
ER -