ID 110902
著者
Jung, Hyunkyung Kyoto Pharmaceutical University
Shimatani, Yuri Kyoto Pharmaceutical University
Hasan, Mahadi Kyoto Pharmaceutical University
Uno, Kohei Kyoto Pharmaceutical University
Hama, Susumu Kyoto Pharmaceutical University
キーワード
flexible nanocarrier
intercellular penetrability
siRNA/PLL polyplexes
資料タイプ
学術雑誌論文
抄録
Various non-viral delivery systems for small interfering RNAs (siRNA) have been developed. Such delivery systems generally exhibit tightly formed spherical structures. While such carriers have demonstrated good transfection activity in mono-layered cell systems, effects against solid tumors are often less apparent and difficult to demonstrate, likely due to the rigid structures of the carriers, which may prevent penetration to deeper regions within tumor tissue. Herein, we developed a flexible nanocarrier (FNC) system that is able to penetrate to deeper regions within tumor tissue. Specifically, we employed previously found flexible polyplexes comprised of siRNA and poly-L-lysine as wick structures for the preparation of FNCs. FNCs were constructed by coating the wick structures with lipids using a liposomal membrane fusion method. The diameters of the resulting FNCs were ca. 170 nm, and the shapes were non-spherical. Lipid coating was confirmed using a nuclease resistance assay. Furthermore, FNCs showed significant RNA interference effects, comparable to Lipofectamine 2000, in a mono-layered cell system. To accelerate tumor penetration, the FNC surface was modified with polyethylene glycol (PEG) and the tight junction opener peptide AT1002. Surface-modified FNCs demonstrated effective penetrability into a cancer spheroid. Thus, we developed a novel and unique tumor-penetrable siRNA FNC system.
掲載誌名
International Journal of Pharmaceutics
ISSN
03785173
cat書誌ID
AA00680771
AA11530828
出版者
Elsevier
516
1-2
開始ページ
258
終了ページ
265
並び順
258
発行日
2016-11-18
備考
© 2016 Elsevier B.V. All rights reserved.
© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
321618
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
著者版
部局
薬学系