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Herein, we describe a novel family of non\u2010covalently stapled self\u2010assembled artificial channels activatable by biocompatible visible light at 442\u2005nm, which enables the co\u2010transport of H<jats:sup>+<\/jats:sup>\/Cl<jats:sup>\u2212<\/jats:sup> across the membrane with H<jats:sup>+<\/jats:sup>\/Cl<jats:sup>\u2212<\/jats:sup> transport selectivity of 6.0. Upon photoirradiation of the caged <jats:bold>C4F\u2010L<\/jats:bold> for 10\u2005min, 90\u2009% of ion transport efficiency can be restored, giving rise to a 10.5\u2010fold enhancement in cytotoxicity against human colorectal cancer cells (IC<jats:sub>50<\/jats:sub>=8.5\u2005\u03bcM). The mechanism underlying cancer cell death mediated by the H<jats:sup>+<\/jats:sup>\/Cl<jats:sup>\u2212<\/jats:sup> channels involves the activation of the caspase\u20059 apoptosis pathway as well as the scarcely reported disruption of the autophagic processes. In the absence of photoirradiation, <jats:bold>C4F\u2010L<\/jats:bold> exhibits minimal toxicity towards normal intestine cells, even at a concentration of 200\u2005\u03bcM.<\/jats:p>","DOI":"10.1002\/anie.202314666","type":"journal-article","created":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T09:10:49Z","timestamp":1697879449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Non\u2010Covalently Stapled H<sup>+<\/sup>\/Cl<sup>\u2212<\/sup> Ion Channels Activatable by Visible Light for Targeted Anticancer Therapy"],"prefix":"10.1002","volume":"63","author":[{"given":"Qishuo","family":"Zhong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences Xiamen University  Xiamen, Fujian 361102 China"},{"name":"Shenzhen Research Institute of Xiamen University  Shenzhen, 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