Asymmetric 1-alkyl-2-acyl phosphatidylcholine: a helper lipid for enhanced non-viral gene delivery.
Asymmetric 1-alkyl-2-acyl phosphatidylcholine: a helper lipid for enhanced non-viral gene delivery.
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DOI：
10.1016/j.ijpharm.2011.06.022
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发表时间：
2012-05-01
影响因子：
5.8
通讯作者：
Szoka, Francis C., Jr.
中科院分区：
文献类型：
--
作者：
Huang, Zhaohua;Li, Weijun;Szoka, Francis C., Jr.
合理设计的不对称烷基酰磷脂酰胆碱（APC）已被合成并评价为非病毒基因传递的辅助脂质。在甘油主链的1位上有一个长脂肪链（C22~C24），在2位上有一个支链脂链（C18），在3位上有一个磷酸胆碱头基团。APC的致熔性取决于烷基链的长度和饱和程度。将阳离子脂质与APC配制成脂质体或纳米脂粒，并评估其稳定性、转染效率和细胞毒性。APC体外转染效率高，细胞毒性低。小的纳米颗粒（小于100纳米）可以用APC通过应用低至0.1%的peg -脂质获得。我们的研究扩展了适合基因转移的辅助脂质类型，并为改进非病毒核酸传递系统指明了途径，而不是传统的阳离子脂质优化。这项工作由NIH拨款EB003008支持。
Rationally designed asymmetrical alkylacyl phosphatidylcholines (APC) have been synthesized and evaluated as helper lipids for non-viral gene delivery. A long aliphatic chain (C22~C24) was introduced at the 1-position of glycerol backbone, a branched lipid chain (C18) at the 2-position, and a phosphocholine head group at the 3-position. The fusogenicity of APC depends on the length and degree of saturation of the alkyl chain. Cationic lipids were formulated with APC as either lipoplexes or nanolipoparticles, and evaluated for their stability, transfection efficiency, and cytotoxicity. APC mediated high in vitro transfection efficiency, and had low cytotoxicity. Small nanolipoparticles (less than 100 nm) can be obtained with APC by applying as low as 0.1% PEG-lipid. Our study extends the type of helper lipids that are suitable for gene transfer and points the way to improve non-viral nucleic acid delivery system other than the traditional cationic lipids optimization. This work is supported by NIH grant EB003008.
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