%0 Journal Article
%T Concentration-Driven Evolution of Adaptive Artificial Ion Channels or Nanopores with Specific Anticancer Activities.
%A Chen Z
%A Xie X
%A Jia C
%A Zhong Q
%A Zhang Q
%A Luo D
%A Cao Y
%A Mu Y
%A Ren C
%J Angew Chem Int Ed Engl
%V 63
%N 17
%D 2024 04 22
%M 38419371
%F 16.823
%R 10.1002/anie.202318811
%X In nature, ceramides are a class of sphingolipids possessing a unique ability to self-assemble into protein-permeable channels with intriguing concentration-dependent adaptive channel cavities. However, within the realm of artificial ion channels, this interesting phenomenon is scarcely represented. Herein, we report on a novel class of adaptive artificial channels, Pn-TPPs, based on PEGylated cholic acids bearing triphenylphosphonium (TPP) groups as anion binding motifs. Interestingly, the molecules self-assemble into chloride ion channels at low concentrations while transforming into small molecule-permeable nanopores at high concentrations. Moreover, the TPP groups endow the molecules with mitochondria-targeting properties, enabling them to selectively drill holes on the mitochondrial membrane of cancer cells and subsequently trigger the caspase 9 apoptotic pathway. The anticancer efficacies of Pn-TPPs correlate with their abilities to form nanopores. Significantly, the most active ensembles formed by P5-TPP exhibits impressive anticancer activity against human liver cancer cells, with an IC50 value of 3.8 μM. While demonstrating similar anticancer performance to doxorubicin, P5-TPP exhibits a selectivity index surpassing that of doxorubicin by a factor of 16.8.