Non‐Covalently Stapled H+/Cl- Ion Channels Activatable by Visible Light for Targeted Anticancer Therapy
Non‐Covalently Stapled H+/Cl- Ion Channels Activatable by Visible Light for Targeted Anticancer Therapy
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DOI：
10.1002/ange.202314666
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Changliang Ren
中科院分区：
文献类型：
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作者：
Qishuo Zhong;Yin Cao;Xiaopan Xie;Yuhang Wu;Zhiqing Chen;Qiuping Zhang;Chunyan Jia;Zhen Wu;Pengyang Xin;Xiaosheng Yan;Zhiping Zeng;Changliang Ren
The development of stimuli-responsive artificial H+/Cl− ion channels, capable of specifically disturbing the intracellular ion homeostasis of cancer cells, presents an intriguing opportunity for achieving high selectivity in cancer therapy. Herein, we describe a novel family of non-covalently stapled self-assembled artificial channels activatable by biocompatible visible light at 442 nm, which enables the co-transport of H+/Cl− across the membrane with H+/Cl− transport selectivity of 6.0. Upon photoirradiation of the caged C4F-L for 10 min, 90 % of ion transport efficiency can be restored, giving rise to a 10.5-fold enhancement in cytotoxicity against human colorectal cancer cells (IC50=8.5 μM). The mechanism underlying cancer cell death mediated by the H+/Cl− channels involves the activation of the caspase 9 apoptosis pathway as well as the scarcely reported disruption of the autophagic processes. In the absence of photoirradiation, C4F-L exhibits minimal toxicity towards normal intestine cells, even at a concentration of 200 μM.
