Cholesterol-stabilized membrane-active nanopores with anticancer activities

• 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
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science; Membranes; Nanopores
• Online Access: https://hdl.handle.net/10356/170821
• Institution: Nanyang Technological University

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 (IC50 = 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.