Ammonium Gemini Surfactants Form Complexes with Model Oligomers of siRNA and dsDNA
Ammonium Gemini Surfactants Form Complexes with Model Oligomers of siRNA and dsDNA
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DOI：
10.3390/ijms20225546
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Kozak, Maciej
中科院分区：
文献类型：
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作者：
Andrzejewska, Weronika;Wilkowska, Michalina;Kozak, Maciej
二聚阳离子表面活性剂（双子型）是一组在基因治疗中作为核酸转染的有效载体（即，siRNA、DNA和质粒DNA）。我们的研究表明，由烷二基-α，ω-双[（氧甲基）二甲基十二烷基铵]氯化物和选定的21碱基对核酸（dsDNA和siRNA）寡聚体组成的脂质复合物的形成。为了研究这些系统的结构和物理化学性质，使用了光学显微镜、圆二色性光谱（CD）、同步辐射小角X射线散射（SR-SAXS）和琼脂糖凝胶电泳（AGE）。所研究的表面活性剂的间隔基团的长度对表面活性剂的络合性能有显着的影响。观察到稳定脂质复合物的最低电荷比（p/n）为1.5，这些脂质复合物最常见的微观结构分别为dsDNA和siRNA的立方相和胶束相。对HeLa细胞的细胞毒性试验表明，表面活性剂的无毒浓度约为10 μ M。研究的双阳离子双子表面活性剂与siRNA和dsDNA寡聚物形成复合物;然而，复合过程对siRNA更有效。因此，这些系统可用作治疗性核酸的转染系统。
Dimeric cationic surfactants (gemini-type) are a group of amphiphilic compounds with potential use in gene therapy as effective carriers for nucleic acid transfection (i.e., siRNA, DNA, and plasmid DNA). Our studies have shown the formation of lipoplexes composed of alkanediyl-alpha,omega-bis[(oxymethyl)dimethyldodecylammonium] chlorides and selected 21-base-pair nucleic acid (dsDNA and siRNA) oligomers. To examine the structure and physicochemical properties of these systems, optical microscopy, circular dichroism spectroscopy (CD), small-angle X-ray scattering of synchrotron radiation (SR-SAXS), and agarose gel electrophoresis (AGE) were used. The lengths of spacer groups of the studied surfactants had a significant influence on the surfactants' complexing properties. The lowest charge ratio (p/n) at which stable lipoplexes were observed was 1.5 and the most frequently occurring microstructure of these lipoplexes were cubic and micellar phases for dsDNA and siRNA, respectively. The cytotoxicity tests on HeLa cells indicated the non-toxic concentration of surfactants to be at approximately 10 mu M. The dicationic gemini surfactants studied form complexes with siRNA and dsDNA oligomers; however, the complexation process is more effective towards siRNA. Therefore these systems could be applied as transfection systems for therapeutic nucleic acids.