文献类型：期刊文献

英文题名：Combination Cancer Treatment: Using Engineered DNAzyme Molecular Machines for Dynamic Inter- and Intracellular Regulation

作者：Qian, Ruo-Can[1];Zhou, Ze-Rui[1];Wu, Yuting[2];Yang, Zhenglin[2];Guo, Weijie[2];Li, Da-Wei[1];Lu, Yi[2]

机构：[1]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Sci Ctr Materiobiol & Dynam Chem, Key Lab Adv Mat,Sch Chem & Mol Engn, Shanghai 200237, Peoples R China;[2]Univ Illinois, Dept Chem, Urbana, IL 61801 USA

年份：2022

卷号：61

期号：49

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20224613106548);WOS:【SCI-EXPANDED(收录号:WOS:000882556800001)】；

基金：This research was supported by the National Natural Science Foundation of China (21977031), the U.S. National Institutes of Health (GM141931), Science and Technology Commission of Shanghai Municipality (2018SHZDZX03), Shanghai Science and Technology Committee (22ZR1416800), and the Fundamental Research Funds for the Central Universities. The authors thank Dr. Bo-Hao Yu at Research Center of Analysis and Test of East China University of Science and Technology for the help on laser scanning confocal microscopy analysis.

语种：英文

外文关键词：DNAzyme; Molecular machine; Dynamic cellular regulation; Combination cancer therapy; Cell apoptosis

摘要：Despite the promise of combination cancer therapy, it remains challenging to develop targeted strategies that are nontoxic to normal cells. Here we report a combination therapeutic strategy based on engineered DNAzyme molecular machines that can promote cancer apoptosis via dynamic inter- and intracellular regulation. To achieve external regulation of T-cell/cancer cell interactions, we designed a DNAzyme-based molecular machine with an aptamer and an i-motif, as the MUC-1-selective aptamer allows the specific recognition of cancer cells. The i-motif is folded under the tumor acidic microenvironment, shortening the intercellular distance. As a result, T-cells are released by metal ion activated DNAzyme cleavage. To achieve internal regulation of mitochondria, we delivered another DNAzyme-based molecular machine with mitochondria-targeted peptides into cancer cells to induce mitochondria aggregation. Our strategy achieved an enhanced killing effect in zinc deficient cancer cells.