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Despite their biological importance, mimicking proton\u2010activated functionality in artificial ion channels remains a significant challenge. Here, we present a novel class of proton\u2010activated artificial ion channels built from self\u2010assembled peptide chains integrated into a pH\u2010responsive 2,2\u2032\u2010bipyridine scaffold. Protonation induces a conformational switch in the channel\u2010forming units, promoting one\u2010dimensional self\u2010assembly and subsequent hydrophobic packing into functional channels capable of transporting small molecules. As extracellular pH decreases from 7.4 to 6.5,\n                    <jats:bold>C\u2010FF<\/jats:bold>\n                    exhibits a 10.3\u2010fold enhancement in cytotoxicity against human colorectal carcinoma cells, boosting an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 2.8\u00a0\u00b5M, mediated through apoptosis induction and cell cycle arrest resulting from disruption of the autophagic process. Significantly,\n                    <jats:bold>C\u2010FF<\/jats:bold>\n                    demonstrates exceptional selectivity for cancer cells, achieving a selectivity index of 8.5, surpassing that of doxorubicin by one order of magnitude while maintaining comparable potency, highlighting its potential as a pH\u2010responsive platform for selective anticancer therapy in acidic tumor microenvironments.\n                  <\/jats:p>","DOI":"10.1002\/anie.202525440","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T06:25:45Z","timestamp":1769667945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Proton\u2010Activated Artificial Channels for pH\u2010Selective Cancer Therapy"],"prefix":"10.1002","volume":"65","author":[{"given":"Daoxin","family":"Luo","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Innovative Drug Target Research State Key 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