Modulation of a membrane lipid lamellar-nonlamellar phase transition by cationic lipids: A measure for transfection efficiency

被引:48
作者
Tenchov, Boris G. [1 ]
Wang, Li [1 ]
Koynova, Rumiana [1 ]
MacDonald, Robert C. [1 ]
机构
[1] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2008年 / 1778卷 / 10期
基金
奥地利科学基金会; 美国国家卫生研究院;
关键词
Cationic lipid; Lipofection; Lipoplex; Phase transition; Inverted hexagonal phase; Cubic phase;
D O I
10.1016/j.bbamem.2008.07.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Synthetic cationic lipids can be used as DNA carriers and are regarded to be the most promising non-viral gene carriers. For this investigation, six novel phosphatidylcholine (PC) cationic derivatives with various hydrophobic moieties were synthesized and their transfection efficiencies for human umbilical artery endothelial cells (HUAEC) were determined. Three compounds with relatively short, myristoleoyl or myristelaicloyl 14:1 chains exhibited very high activity, exceeding by similar to 10 times that of the reference cationic derivative dioleoyl ethyIPC (EDOPC). Noteworthy, cationic lipids with 14:1 hydrocarbon chains have not been tested as DNA carriers in transfection assays previously. The other three lipids, which contained oleoyl 18:1 and longer chains, exhibited moderate to weak transfection activity. Transfection efficiency was found to correlate strongly with the effect of the cationic lipids on the lamellar-to-inverted hexagonal, L-alpha -> H-II, phase conversion in dipalmitoleoyl phosphatidylethanolamine dispersions (DPoPE). X-ray diffraction on binary DPoPE/cationic lipid mixtures showed that the superior transfection agents eliminated the direct L-alpha -> H-II phase transition and promoted formation of an inverted cubic phase between the L-alpha and H-II phases. In contrast, moderate and weak transfection agents retained the direct L-alpha -> H-II transition but shifted to higher temperatures than that of pure DPoPE, and induced cubic phase formation at a later stage. On the basis of current models of lipid membrane fusion, promotion of a cubic phase by the high-efficiency agents may be considered as an indication that their high transfection activity results from enhanced lipoplex fusion with cellular membranes. The distinct, well-expressed correlation established between transfection efficiency of a cationic lipid and the way it modulates nonlamellar phase formation of a membrane lipid could be useful as a criterion to assess the quality of lipid carriers and for rational design of new and superior nucleotide delivery agents. (c) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:2405 / 2412
页数:8
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