Niosomes based on synthetic cationic lipids for gene delivery: the influence of polar head-groups on the transfection efficiency in HEK-293, ARPE-19 and MSC-D1 cells
Niosomes based on synthetic cationic lipids for gene delivery: the influence of polar head-groups on the transfection efficiency in HEK-293, ARPE-19 and MSC-D1 cells
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DOI：
10.1039/c4ob02087a
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发表时间：
2015-01-01
影响因子：
3.2
通讯作者：
Pedraz, J. L.
中科院分区：
文献类型：
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作者：
Ojeda, E.;Puras, G.;Pedraz, J. L.
我们设计了基于三种脂质的囊泡，它们仅在极性头基团上不同，以分析它们对转染效率的影响。这些脂质通过小角X射线散射表征，然后掺入到囊泡中，囊泡在pK（α）、大小、ζ电位、形态和物理稳定性方面表征。在添加质粒后获得Nioplexes。选择不同的比率（w/w）来分析该参数对尺寸、电荷以及浓缩、释放和保护DNA的能力的影响。在HEK-293、ARPE-19和MSC-D1细胞中进行体外转染实验。我们的研究结果表明，阳离子头基的化学组成明显影响的物理化学参数的泡囊，特别是转染效率。只有基于具有二甲基氨基头基的阳离子脂质（脂质3）的类囊泡在与它们的对应物氨基（脂质1）和三肽头基（脂质2）相比时显示出转染能力。关于细胞活力，我们清楚地观察到基于阳离子脂质3的纳米复合物比它们的对应物具有更有害的作用，特别是在20/1和30/1比率的ARPE-19细胞中。类似的研究可以扩展到其他系列的阳离子脂质体，以便在安全有效的非病毒基因载体的研究中取得进展。
We designed niosomes based on three lipids that differed only in the polar-head group to analyze their influence on the transfection efficiency. These lipids were characterized by small-angle X-ray scattering before being incorporated into the niosomes which were characterized in terms of pK(a), size, zeta potential, morphology and physical stability. Nioplexes were obtained upon the addition of a plasmid. Different ratios (w/w) were selected to analyze the influence of this parameter on size, charge and the ability to condense, release and protect the DNA. In vitro transfection experiments were performed in HEK-293, ARPE-19 and MSC-D1 cells. Our results show that the chemical composition of the cationic head-group clearly affects the physicochemical parameters of the niosomes and especially the transfection efficiency. Only niosomes based on cationic lipids with a dimethyl amino head group (lipid 3) showed a transfection capacity when compared with their counterparts amino (lipid 1) and tripeptide head-groups (lipid 2). Regarding cell viability, we clearly observed that nioplexes based on the cationic lipid 3 had a more deleterious effect than their counterparts, especially in ARPE-19 cells at 20/1 and 30/1 ratios. Similar studies could be extended to other series of cationic lipids in order to progress in the research on safe and efficient non-viral vectors for gene delivery purposes.