{Reference Type}: Journal Article
{Title}: Non-Covalently Stapled H+ /Cl- Ion Channels Activatable by Visible Light for Targeted Anticancer Therapy.
{Author}: Zhong Q;Cao Y;Xie X;Wu Y;Chen Z;Zhang Q;Jia C;Wu Z;Xin P;Yan X;Zeng Z;Ren C;
{Journal}: Angew Chem Int Ed Engl
{Volume}: 63
{Issue}: 3
{Year}: 2024 01 15
{Factor}: 16.823
{DOI}: 10.1002/anie.202314666
{Abstract}: 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.