脱氧核酶
适体
癌细胞
细胞内
化学
细胞生物学
线粒体
劈理(地质)
肿瘤微环境
癌症
细胞凋亡
纳米技术
癌症研究
生物化学
生物
肿瘤细胞
分子生物学
DNA
材料科学
遗传学
古生物学
断裂(地质)
作者
Ruo‐Can Qian,Ze-Rui Zhou,Yuting Wu,Zhenglin Yang,Weijie Guo,Dawei Li,Yi Lu
标识
DOI:10.1002/anie.202210935
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.
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