Cholesterol-stabilized membrane-active nanopores with anticancer activities

Cholesterol-enhanced pore formation is one evolutionary means cholesterol-free bacterial cells utilize to specifically target cholesterol-rich eukaryotic cells, thus escaping the toxicity these membrane-lytic pores might have brought onto themselves. Here, we present a class of artificial cholestero...

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Bibliographic Details
Published in:Nature communications 2022-10, Vol.13 (1), p.5985-5985, Article 5985
Main Authors: Shen, Jie, Gu, Yongting, Ke, Lingjie, Zhang, Qiuping, Cao, Yin, Lin, Yuchao, Wu, Zhen, Wu, Caisheng, Mu, Yuguang, Wu, Yun-Long, Ren, Changliang, Zeng, Huaqiang
Format: Article
Language:English
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Acids
Anticancer properties
Antitumor activity
Channel gating
Channel pores
Cholesterol
Hepatocellular carcinoma
Hepatocytes
Humanities and Social Sciences
Ions
Laboratories
Lipids
Liver cancer
Membranes
Modularity
multidisciplinary
Pore formation
Pore size
Science
Science (multidisciplinary)
Selectivity
Toxicity
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Summary:Cholesterol-enhanced pore formation is one evolutionary means cholesterol-free bacterial cells utilize to specifically target cholesterol-rich eukaryotic cells, thus escaping the toxicity these membrane-lytic pores might have brought onto themselves. Here, we present a class of artificial cholesterol-dependent nanopores, manifesting nanopore formation sensitivity, up-regulated by cholesterol of up to 50 mol% (relative to the lipid molecules). The high modularity in the amphiphilic molecular backbone enables a facile tuning of pore size and consequently channel activity. Possessing a nano-sized cavity of ~ 1.6 nm in diameter, our most active channel Ch-C1 can transport nanometer-sized molecules as large as 5(6)-carboxyfluorescein and display potent anticancer activity (IC 50  = 3.8 µM) toward human hepatocellular carcinomas, with high selectivity index values of 12.5 and >130 against normal human liver and kidney cells, respectively. Bacterial cells utilize cholesterol-enhanced pore formation to specifically target eukaryotic cells. Here, the authors present a class of bio-inspired, cholesterol-enhanced nanopores which display anticancer activities in vitro.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-33639-5