Synthesis and properties of novel tetraalkyl cationic lipids
Synthesis and properties of novel tetraalkyl cationic lipids
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DOI：
10.1021/bc0101259
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发表时间：
2002-05-01
影响因子：
4.7
通讯作者：
Cullis, PR
中科院分区：
文献类型：
--
作者：
Gaucheron, J;Wong, T;Cullis, PR
本文介绍了一类新的二价四烷基阳离子脂类的合成、物理性质和转染力。这些阳离子脂类是NN-二烯基-N，N-二甲基氯化铵(DODAC)的二聚体，由长度为3或6个碳的碳氢链连接(分别为TODMAC3和TODMAC6)。结果表明，与DODAC相比，TODMAC6在制备成DNA-阳离子脂质复合体时具有更好的转染性。当阳离子脂与DNA的电荷比为2或更高时，可以观察到这些改进的转染力。研究还表明，与DODAC相比，TODMAC6在含有阴离子脂质的混合物中诱导非双层结构的能力相当或更强。这与阳离子脂类与阴离子脂类混合时诱导非双层结构的能力与其转染力相关的假设是一致的。另一方面，含有TODMAC3的络合物表现出比DODAC更低的转染势，这一行为与限制与阴离子脂形成离子对的空间效应一致。结论：TODMAC6作为体外和体内的转染剂具有潜在的应用前景，根据阳离子脂类诱导非双层结构的能力设计阳离子脂类为合成新的阳离子脂类提供了有用的指导。
The synthesis, physical properties, and transfection potencies of two representives of a new class of divalent, tetraalkyl cationic lipids is described. These cationic lipids are dimers of NN-Dioleyl-N,N-dimethylammonium chloride (DODAC) joined by a hydrocarbon tether three or six carbons in length (TODMAC3 and TODMAC6, respectively). It is shown that TODMAC6 can display improved transfection properties in comparison to DODAC when formulated into plasmid DNA-cationic lipid complexes. These improved transfection potencies are observed at cationic lipid to DNA charge ratios of two or higher. It is also shown that TODMAC6 exhibits equivalent or improved ability (as compared to DODAC) to induce nonbilayer structure in mixtures with anionic lipid. This is consistent with the hypothesis that the ability of cationic lipids to induce nonbilayer structures when mixed with anionic lipids is correlated to their transfection potency. Complexes containing TODMAC3 on the other hand exhibit lower transfection potencies than achieved with DODAC, behavior that is consistent with steric effects limiting the formation of ion pairs with anionic lipids. It is concluded that TODMAC6 exhibits potential as a transfection agent for in vitro and in vivo use and that the design of cationic lipids according to their ability to induce nonbilayer structure provides a useful guide for synthesis of new cationic lipids.