Cationic Lipid-Coated Polyplexes (Lipopolyplexes) for DNA and Small RNA Delivery
Cationic Lipid-Coated Polyplexes (Lipopolyplexes) for DNA and Small RNA Delivery
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DOI：
10.1007/978-1-4939-3718-9_12
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Aigner, Achim
中科院分区：
文献类型：
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作者：
Ewe, Alexander;Aigner, Achim
核酸（NA）如用于细胞转染的DNA或用于基因敲低的siRNA的递送对于体外研究以及体内应用是主要关注的。其他小RNA分子如miRNA或miRNA抑制剂（antimiR）也是如此。重要的非病毒基因递送载体包括脂质体和阳离子聚合物。关于阳离子聚合物，聚乙烯亚胺（PEI）通过充当纳米级递送平台（聚合复合物）而被充分确立用于递送NA。它们与包含不同磷脂的脂质体的组合导致形成脂聚复合物，并且可以通过组合脂质系统的有利性质来进一步改善它们的功效和生物相容性（高稳定性，有效的细胞摄取，低细胞毒性）和PEI（NA缩合，促进内体释放）。在本章中，给出了含有不同脂质体和某些支化或线性低分子量PEI的最佳脂质多聚物组合物。重要的是，某些脂聚复合物在室温（RT）下、在血清存在下和雾化后长时间储存时保持其生物活性和物理化学完整性，从而将其有用性扩展到体内的各种应用。
The delivery of nucleic acids (NA) like DNA for cell transfection or siRNAs for gene knockdown is of major interest for in vitro studies as well as for applications in vivo. The same is true for other small RNA molecules like miRNAs or miRNA inhibitors (antimiRs). Important nonviral gene delivery vectors include liposomes and cationic polymers. With regard to cationic polymers, polyethylenimines (PEIs) are well established for the delivery of NA, by acting as nanoscale delivery platforms (polyplexes). Their combination with liposomes comprising different phospholipids leads to the formation of lipopolyplexes and can further improve their efficacy and biocompatibility, by combining the favorable properties of lipid systems (high stability, efficient cellular uptake, low cytotoxicity) and PEI (NA condensation, facilitated endosomal release).In this chapter, optimal lipopolyplex compositions containing different liposomes and certain branched or linear low-molecular weight PEIs are given. This also includes optimal parameters for lipopolyplex generation, based on various PEIs, N/P ratios, lipids, lipid/PEI ratios, and preparation conditions.Importantly, certain lipopolyplexes retain their biological activity and physicochemical integrity upon prolonged storage at room temperature (RT), in the presence of serum and upon nebulization, thus extending their usefulness toward various applications in vivo.