Enhanced siRNA delivery using cationic liposomes with new polyarginine-conjugated PEG-lipid
Enhanced siRNA delivery using cationic liposomes with new polyarginine-conjugated PEG-lipid
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DOI：
10.1016/j.ijpharm.2010.03.047
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发表时间：
2010-06-15
影响因子：
5.8
通讯作者：
Park, Jeong-Sook
中科院分区：
文献类型：
--
作者：
Kim, Hyun-Ki;Davaa, Enkhzaya;Park, Jeong-Sook
基于小干扰RNA(SiRNA)的基因治疗已经成为一种令人兴奋的新的治疗方法。然而，细胞摄取不足和稳定性差限制了它的用途。在这里，我们报告了通过使用含有一种新的聚乙二醇脂类的阳离子脂质体有效地传递siRNA。合成了一种新型脂质--聚L-精氨酸偶联聚乙二醇脂。用核磁共振氢谱和凝胶渗透色谱(GPC)证实了氨基酸偶联聚乙二醇脂的合成。以阳离子脂类1，2-二油酰基-3-三甲基丙烷、1，2-dioleoyl-sn-glycero-3-phosphoethanolaminepropane(DOPE)、胆固醇(CHOL)和聚乙二醇乙二醇酯(PLR-PEG4)为原料，制备阳离子脂质体作为非病毒载体。考察了阳离子脂质体的物理化学性质。以GFP siRNA为模型siRNA，检测阳离子脂质体介导的siRNA传递效率。在优化的脂类组成条件下，脂质体可以提高给药效率，降低细胞毒性。使用新型聚乙二醇脂的阳离子脂质体(PLR-PEG)不仅增强了siRNA在细胞内的转运，而且降低了对H4II-E和HepG2细胞的细胞毒作用。新型阳离子脂质体携带的GFP siRNA能有效降低GFP基因的蛋白表达水平。这些结果表明，新型阳离子脂质体可用于有效地传递siRNA治疗药物。(C)2010爱思唯尔B.V.保留所有权利。
Gene therapy based on small interfering RNA (siRNA) has emerged as an exciting new therapeutic approach. However, insufficient cellular uptake and poor stability have limited its usefulness. Here, we report efficient delivery of siRNA via the use of cationic liposomes that contain a new PEG-lipid. The new lipid, poly-L-arginine-conjugated polyethylene glycol (PLR-PEG), was synthesized. To confirm the synthesis of the amino acid-conjugated PEG-lipid, H-1 NMR and gel permeation chromatography (GPC) were performed. Cationic liposomes as non-viral vectors were formulated using the cationic lipids 1,2-dioleoy1-3-trimethylammonium propane (DOTAP), 1,2-dioleoyl-sn-glycero-3-phosphoethanolaminepropane (DOPE), cholesterol (Chol) and PLR-PEG. Physicochemical properties of cationic liposomes were investigated. A GFP siRNA was used as a model siRNA to test the efficiency of cationic liposome-mediated siRNA delivery. The liposomes could enhance delivery efficiency and decrease cytotoxicity at an optimized lipid composition. The new cationic liposome formulation using a new PEG-lipid (PLR-PEG) showed not only enhanced intracellular delivery of siRNA but also decreased cytotoxicity in H4II-E and HepG2 cell lines. The GFP siRNA delivered by new cationic liposomes using PLR-PEG was effective in reducing the GFP protein expression levels of the gene. These results suggest that the new cationic liposomes could be used for efficient delivery of siRNA therapeutics. (C) 2010 Elsevier B.V. All rights reserved.