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基于甘油单油酸酯的纳米载体用于 siRNA 的体外递送。

Glycerol monooleate-based nanocarriers for siRNA delivery in vitro.

机构信息

CSIRO Materials Science and Engineering, Bayview Avenue, Clayton, Victoria 3168, Australia.

出版信息

Mol Pharm. 2012 Sep 4;9(9):2450-7. doi: 10.1021/mp200662f. Epub 2012 Aug 10.

Abstract

We present studies of the delivery of short interfering ribonucleic acid (siRNA) into a green fluorescent protein (GFP) expressing cell line, using lipid nanocarriers in cubic lyotropic liquid crystal form. These carriers are based on glycerol monooleate (GMO) and employ the use of varying concentrations of cationic siRNA binding lipids. The essential physicochemical parameters of the cationic lipid/GMO/siRNA complexes such as particle size, ζ otential, siRNA uptake stability, lyotropic mesophase behavior, cytotoxicity,and gene silencing efficiency were systematically assessed. We find that the lipid nanocarriers were effectively taken up by mammalian cells and that their siRNA payload was able to induce gene silencing in vitro. More importantly, it was found that the nonlamellar structure of some of the lipid nanocarrier formulations were more effective at gene silencing than their lamellar structured counterparts. The development of cationic lipid functionalized nonlamellar GMO-based nanostructured nanoparticles may lead to improved siRNA delivery vehicles.

摘要

我们研究了使用立方各向同性液晶形式的脂质纳米载体将短干扰核糖核酸 (siRNA) 递送到表达绿色荧光蛋白 (GFP) 的细胞系中的情况。这些载体基于甘油单油酸酯 (GMO),并采用不同浓度的阳离子 siRNA 结合脂质。系统评估了阳离子脂质/GMO/siRNA 复合物的重要理化参数,如粒径、ζ 电位、siRNA 摄取稳定性、各向同性介相行为、细胞毒性和基因沉默效率。我们发现脂质纳米载体可被哺乳动物细胞有效摄取,其 siRNA 有效负载可在体外诱导基因沉默。更重要的是,发现一些脂质纳米载体制剂的非层状结构比其层状结构更有效地进行基因沉默。阳离子脂质功能化非层状 GMO 基纳米结构纳米颗粒的开发可能会导致改进的 siRNA 递药载体。

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