学術雑誌論文 Development of flexible nanocarriers for siRNA delivery into tumor tissue

Jung, Hyunkyung  ,  Shimatani, Yuri  ,  Hasan, Mahadi  ,  Uno, Kohei  ,  Hama, Susumu  ,  Kogure, Kentaro

516 ( 1-2 )  , pp.258 - 265 , 2016-11-18 , Elsevier
ISSN:03785173
NII書誌ID(NCID):AA00680771AA11530828
内容記述
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.
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http://repo.lib.tokushima-u.ac.jp/files/public/11/110902/20171117163744702724/ijpharm_516_1-2_258.pdf

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