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Cholesterol-stabilized membrane-active nanopores with anticancer activities

Author

Listed:
  • Jie Shen

    (Xiamen University
    Fuzhou University)

  • Yongting Gu

    (Xiamen University)

  • Lingjie Ke

    (Xiamen University)

  • Qiuping Zhang

    (Xiamen University)

  • Yin Cao

    (Xiamen University)

  • Yuchao Lin

    (Xiamen University)

  • Zhen Wu

    (Xiamen University)

  • Caisheng Wu

    (Xiamen University)

  • Yuguang Mu

    (Nanyang Technological University)

  • Yun-Long Wu

    (Xiamen University)

  • Changliang Ren

    (Xiamen University
    Shenzhen Research Institute of Xiamen University)

  • Huaqiang Zeng

    (Fuzhou University)

Abstract

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.

Suggested Citation

  • Jie Shen & Yongting Gu & Lingjie Ke & Qiuping Zhang & Yin Cao & Yuchao Lin & Zhen Wu & Caisheng Wu & Yuguang Mu & Yun-Long Wu & Changliang Ren & Huaqiang Zeng, 2022. "Cholesterol-stabilized membrane-active nanopores with anticancer activities," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33639-5
    DOI: 10.1038/s41467-022-33639-5
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    References listed on IDEAS

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