In:
Angewandte Chemie, Wiley, Vol. 136, No. 17 ( 2024-04-22)
Abstract:
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‐TPP s, 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‐TPP s 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 IC 50 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.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.v136.17
DOI:
10.1002/ange.202318811
Language:
English
Publisher:
Wiley
Publication Date:
2024
detail.hit.zdb_id:
505868-5
detail.hit.zdb_id:
506609-8
detail.hit.zdb_id:
514305-6
detail.hit.zdb_id:
505872-7
detail.hit.zdb_id:
1479266-7
detail.hit.zdb_id:
505867-3
detail.hit.zdb_id:
506259-7
Permalink