Modulation of pyridinium cationic lipid-DNA complex properties by pyridinium gemini surfactants and its impact on lipoplex transfection properties.
Modulation of pyridinium cationic lipid-DNA complex properties by pyridinium gemini surfactants and its impact on lipoplex transfection properties.
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DOI：
10.1021/mp4005035
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发表时间：
2014-02-03
影响因子：
4.9
通讯作者：
Ilies MA
中科院分区：
文献类型：
--
作者：
Sharma VD;Lees J;Hoffman NE;Brailoiu E;Madesh M;Wunder SL;Ilies MA
该研究展示了将阳离子 Gemini 表面活性剂混合到阳离子脂质双层中的效果及其对质粒 DNA 压缩和递送过程的影响。使用 nanoDSC、动态光散射、zeta 电位和电泳迁移率测量，以及转染（2D 和 3D）和活力测定，我们确定了受 Gemini 表面活性剂添加影响的脂质双层、脂质体和脂质复合物的主要理化参数。我们还将阳离子双层组成与 DNA 压缩过程的动力学以及所得核酸复合物的转染效率、细胞毒性和内化机制相关联。我们发现，将双子表面活性剂混合到阳离子双层中可以使超分子组装体流化，减少完全压缩质粒DNA所需的正电荷量，并且在某些情况下改变脂质复合物的内化机制。由阳离子双子表面活性剂和脂质衍生的精选三元脂质复合物的转染效率比相应二元脂质复合物的转染效率高出数倍，也超过了标准转染系统。发现双子表面活性剂对阳离子双层的形成和动态的总体影响在很大程度上取决于共脂质的存在、它们的性质和存在于脂质复合物中的量。该研究证实了将吡啶鎓双子表面活性剂和阳离子脂质的特定性质协同结合的可能性，以获得有效的合成转染系统，其细胞毒性可忽略不计，可用于治疗基因递送。
The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact towards plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viability assays, we identified the main physicochemical parameters of the lipid bilayers, liposomes and lipoplexes that are affected by the gemini surfactant addition. We also correlated the cationic bilayer composition with the dynamics of the DNA compaction process, and with transfection efficiency, cytotoxicity and internalization mechanism of the resultant nucleic acid complexes. We found that blending of gemini surfactant into the cationic bilayers fluidized the supramolecular assemblies, reduced the amount of positive charge required to fully compact the plasmid DNA and, in certain cases, changed the internalization mechanism of the lipoplexes. Transfection efficiency of select ternary lipoplexes derived from cationic gemini surfactants and lipids was several times superior to transfection efficiency of corresponding binary lipoplexes, also surpassing standard transfection systems. The overall impact of gemini surfactants into the formation and dynamic of cationic bilayers was found to depend heavily on the presence of co-lipids, their nature and amount present into lipoplexes. The study confirmed the possibility of combining the specific properties of pyridinium gemini surfactants and cationic lipids synergistically for obtaining efficient synthetic transfection systems with negligible cytotoxicity useful for therapeutic gene delivery.
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影响因子：
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作者：
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DOI：
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发表时间：
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