Endocytic pathway and resistance to cholesterol depletion of cholesterol derived cationic lipids for gene delivery

Yun Ui Bae; Bieong Kil Kim; Jong Won Park; Young Bae Seu; Kyung Oh Doh

doi:10.1021/mp300458h

Endocytic pathway and resistance to cholesterol depletion of cholesterol derived cationic lipids for gene delivery

Yun Ui Bae, Bieong Kil Kim, Jong Won Park, Young Bae Seu, Kyung Oh Doh

School of Life Science and Biotechnology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	3579-3585
Number of pages	7
Journal	Molecular Pharmaceutics
Volume	9
Issue number	12
DOIs	https://doi.org/10.1021/mp300458h
State	Published - 3 Dec 2012

Keywords

cholesterol
endocytic pathway
gene delivery
nonviral vector

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10.1021/mp300458h

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title = "Endocytic pathway and resistance to cholesterol depletion of cholesterol derived cationic lipids for gene delivery",

abstract = "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.",

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T1 - Endocytic pathway and resistance to cholesterol depletion of cholesterol derived cationic lipids for gene delivery

AU - Bae, Yun Ui

AU - Kim, Bieong Kil

AU - Park, Jong Won

AU - Seu, Young Bae

AU - Doh, Kyung Oh

PY - 2012/12/3

Y1 - 2012/12/3

N2 - 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.

AB - 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.

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KW - gene delivery

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Endocytic pathway and resistance to cholesterol depletion of cholesterol derived cationic lipids for gene delivery

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