中国科学院高能物理研究所尹文艳团队报道了配位驱动自组装策略激活铜单原子纳米酶催化肿瘤特异性治疗。相关研究成果发表在2023年2月6日出版的《美国化学会杂志》。

如何优化纳米酶的类酶催化活性以提高其适用性已成为一个巨大的挑战。

该文中，研究人员提出了一种l-半胱氨酸（l-Cys）配位驱动的自组装策略，以激活聚乙烯吡咯烷酮（PVP）修饰的Cu单原子纳米酶MoOx-Cu-Cys（表示为MCCP-SAzymes），用于催化肿瘤特异性治疗。MCCP的Cu单原子含量可以合理调节至10.10wt%，激活MoOx纳米颗粒的过氧化氢酶（CAT）样活性，以催化酸性微环境中H₂O₂的分解，从而增加O₂的产生。令人兴奋的是，MCCP的最大CAT样催化效率比典型MnO₂纳米酶高138倍，并且表现出比天然过氧化氢酶高14.3倍的亲和力，如稳态动力学所示。

研究人员验证了定义明确的l-Cys-Cu··O活性位点通过密度泛函理论计算揭示的l-Cys桥加速电子从Cys-Cu到MoOx的转移，优化了CAT样活性，以匹配天然过氧化氢酶的活性位点。同时，MCCP中的高负载Cu单原子也能够通过类似芬顿的反应生成OH。此外，在X射线照射下，MCCP将O₂转化为¹O₂进行级联放射动力学治疗，从而促进多种活性氧（ROS）进行放射增敏，从而实现显著的抗肿瘤效果。

附：英文原文

Title: Coordination-Driven Self-Assembly Strategy-Activated Cu Single-Atom Nanozymes for Catalytic Tumor-Specific Therapy

Author: Jie Zhou, Deting Xu, Gan Tian, Qian He, Xiao Zhang, Jing Liao, Linqiang Mei, Lei Chen, Lizeng Gao, Lina Zhao, Guoping Yang, Wenyan Yin, Guangjun Nie, Yuliang Zhao

Issue&Volume: February 6, 2023

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 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.

DOI: 10.1021/jacs.2c13597

Source: https://pubs.acs.org/doi/10.1021/jacs.2c13597