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Endocytic Pathway and Resistance to Cholesterol Depletion of Cholesterol Derived Cationic Lipids for Gene Delivery

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journal contribution
posted on 03.12.2012, 00:00 authored by Yun-Ui Bae, Bieong-Kil Kim, Jong-Won Park, Young-Bae Seu, Kyung-Oh Doh
Cholesterol-based cationic lipids have been widely used because of biocompatibility and serum resistance. However, the reason for the effectiveness of cholesterol-based cationic lipids remains unclear. We compared the transfection route of CHOL-E, a cholesterol-based cationic lipid having an amine head and an ether linker, with that of DOTAP. The luciferase assay with chemical inhibitors and microscopic observation of pathway markers revealed that clathrin mediated endocytosis is the main pathway for CHOL-E and DOTAP. However, CHOL-E showed resistance to cholesterol depletion by methyl-β-cyclodextrin. Furthermore, CHOL-E recovered the transfection efficiency of DOTAP from cholesterol depletion. These results suggested that superior transfection of CHOL-E might be partly derived from effects on the cell membrane.