In:
Angewandte Chemie International Edition, Wiley, Vol. 63, No. 3 ( 2024-01-15)
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 (IC 50 =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.
Type of Medium:
Online Resource
ISSN:
1433-7851
,
1521-3773
DOI:
10.1002/anie.202314666
Language:
English
Publisher:
Wiley
Publication Date:
2024
detail.hit.zdb_id:
2011836-3
detail.hit.zdb_id:
123227-7