Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, People's Republic of China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
J Am Chem Soc. 2020 Mar 18;142(11):5177-5183. doi: 10.1021/jacs.9b12873. Epub 2020 Mar 6.
The insufficient intracellular HO level in tumor cells is closely associated with the limited efficacy of chemodynamic therapy (CDT). Despite tremendous efforts, engineering CDT agents with a straightforward and secure HO supplying ability remains a great challenge. Inspired by the balance of HO generation and elimination in cancer cells, herein, a nanozyme-based HO homeostasis disruptor is fabricated to elevate the intracellular HO level through facilitating HO production and restraining HO elimination for enhanced CDT. In the formulation, the disruptor with superoxide dismutase-mimicking activity can convert O to HO, promoting the production of HO. Simultaneously, the suppression of catalase activity and depletion of glutathione by the disruptor weaken the transformation of HO to HO. Thus, the well-defined system could perturb the HO balance and give rise to the accumulation of HO in cancer cells. The raised HO level would ultimately amplify the Fenton-like reaction-based CDT efficiency. Our work not only paves a way to engineer alternative CDT agents with a HO supplying ability for intensive CDT but also provides new insights into the construction of bioinspired materials.
肿瘤细胞中 HO 水平不足与化学动力学治疗（CDT）的疗效有限密切相关。尽管已经做出了巨大的努力，但工程设计具有简单而安全的 HO 供应能力的 CDT 试剂仍然是一个巨大的挑战。受癌细胞中 HO 生成和消除平衡的启发，本文构建了一种基于纳米酶的 HO 动态平衡破坏剂，通过促进 HO 的生成和抑制 HO 的消除来提高细胞内 HO 水平，从而增强 CDT。在配方中，具有模拟超氧化物歧化酶活性的破坏剂可以将 O 转化为 HO，从而促进 HO 的生成。同时，破坏剂对过氧化氢酶活性的抑制和谷胱甘肽的耗竭会削弱 HO 向 HO 的转化。因此，这个明确的系统可以打破 HO 的平衡，导致 HO 在癌细胞中的积累。升高的 HO 水平最终会放大基于芬顿样反应的 CDT 效率。我们的工作不仅为设计具有 HO 供应能力的替代 CDT 试剂以进行强化 CDT 治疗开辟了道路，也为仿生材料的构建提供了新的思路。
