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Relationship Between the Physicochemical Properties of Lipid Nanoparticles and the Quality of siRNA Delivery to Liver Cells

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タイトル: Relationship Between the Physicochemical Properties of Lipid Nanoparticles and the Quality of siRNA Delivery to Liver Cells
著者: Sato, Yusuke 著作を一覧する
Hatakeyama, Hiroto 著作を一覧する
Hyodo, Mamoru 著作を一覧する
Harashima, Hideyoshi 著作を一覧する
発行日: 2016年 4月
出版者: Nature Publishing Group
誌名: Molecular therapy
巻: 24
号: 4
開始ページ: 788
終了ページ: 795
出版社 DOI: 10.1038/mt.2015.222
抄録: While a variety of short interfering RNA (siRNA) delivery compounds have been developed, a deep understanding of the key parameters that determine the quality of siRNA delivery are not known with certainty. Therefore, an understanding of the factors required for the efficient, selective, and safe delivery of siRNA is a great challenge for successful siRNA delivery. Herein, we report on the development of two pH-sensitive cationic lipids and their use in examining the impact of the acid dissociation constant (pK(a)) value, lipase sensitivity and the size of lipid nanoparticles on the biodistribution, and efficiency and cell specificity of gene silencing in the liver. An increase in the pK(a) value resulted in a significant change in the intrahepatic localization of siRNA and gene-silencing efficiency in hepatocytes and liver sinusoidal endothelial cells (LSECs). The sensitivity of the pH-sensitive cationic lipid to lipases was a major factor in achieving hepatocyte-specific gene silencing. Increasing the particle size can improve the LSEC specificity of gene silencing. As a consequence, we succeeded in developing both a highly efficient, hepatocyte-specific formulation, and the most efficacious LSEC-targeted formulation reported to date. These findings will facilitate the development of more sophisticated siRNA delivery systems.
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/62957
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 佐藤 悠介

 

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