Cholesterol-stabilized membrane-active nanopores with anticancer activities.
Cholesterol-stabilized membrane-active nanopores with anticancer activities.
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DOI：
10.1038/s41467-022-33639-5
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发表时间：
2022-10-10
影响因子：
16.6
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中科院分区：
文献类型：
--
作者：
胆固醇增强孔形成是一种进化手段，无胆固醇细菌细胞利用它专门针对富含胆固醇的真核细胞，从而逃避这些膜裂解孔可能给自己带来的毒性。在这里，我们提出了一类人工胆固醇依赖的纳米孔，表现出纳米孔形成的敏感性，被胆固醇上调高达50 mol%（相对于脂质分子）。两亲性分子骨架的高模块性使得孔隙大小和通道活性易于调整。我们最活跃的通道Ch-C1具有直径约1.6 nm的纳米腔，可以运输5(6)-羧基荧光素纳米大小的分子，并对人肝细胞癌显示出强大的抗癌活性（IC50 = 3.8µM），对正常人肝脏和肾脏细胞的选择性指数分别为12.5和bbb130。细菌细胞利用胆固醇增强的孔形成特异性地针对真核细胞。在这里，作者提出了一类生物启发，胆固醇增强纳米孔，在体外显示抗癌活性。
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. 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.
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影响因子：
3.4
作者：
Coghi, Paolo;Yaremenko, Ivan A.;Terent'ev, Alexander O.
通讯作者：
Terent'ev, Alexander O.
影响因子：
16.6
作者：
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通讯作者：
Bartik, Kristin
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通讯作者：
Huczynski, Adam
影响因子：
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作者：
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通讯作者：
Ghadiri, MR
影响因子：
15
作者：
Choi, Ye Rin;Lee, Bom;Jeong, Kyu-Sung
通讯作者：
Jeong, Kyu-Sung