Lipid nanoparticles for hepatic delivery of small interfering RNA.
Lipid nanoparticles for hepatic delivery of small interfering RNA.
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DOI：
10.1016/j.biomaterials.2012.05.002
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发表时间：
2012-09
期刊：
影响因子：
14
通讯作者：
Lee, Ly J.
中科院分区：
文献类型：
--
作者：
Yu, Bo;Hsu, Shu-Hao;Zhou, Chenguang;Wang, Xinmei;Terp, Megan C.;Wu, Yun;Teng, Lesheng;Mao, Yicheng;Wang, Feng;Xue, Weiming;Jacob, Samson T.;Ghoshal, Kalpana;Lee, Robert J.;Lee, Ly J.
Clinical application of small interfering RNA (siRNA) requires safe and efficient delivery in vivo. Here, we report the design and synthesis of lipid nanoparticles (LNPs) for siRNA delivery based on cationic lipids with multiple tertiary amines and hydrophobic linoleyl chains. LNPs incorporating the lipid containing tris(2-aminoethyl)amine (TREN) and 3 linoleyl chain, termed TRENL3, were found to have exceptionally high siRNA transfection efficacy that was markedly superior to lipofectamine, a commercial transfection agent. In addition, inclusion of polyunsaturated fatty acids, such as linoleic acid and linolenic acids in the formulation further enhanced the siRNA delivery efficiency. TRENL3 LNPs were further shown to transported siRNA into the cytosol primarily via macropinocytosis rather than clathrin-mediated endocytosis. The new LNPs have demonstrated preferential uptake by the liver and hepatocellular carcinoma in mice, thereby leading to high siRNA gene silencing activity. These data suggest potential therapeutic applications of TRENL3 mediated delivery of siRNA for liver diseases.
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影响因子：
4.5
作者：
Lin, Xiaoyu;Li, Leiming;Shen, Yu
通讯作者：
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影响因子：
12.4
作者：
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通讯作者：
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DOI：
10.1038/nrd2310
发表时间：
2007-06
期刊：
Nature reviews. Drug discovery
影响因子：
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作者：
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通讯作者：
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影响因子：
14
作者：
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通讯作者：
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影响因子：
10.8
作者：
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通讯作者：
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