Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System
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概要
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We recently developed a multifunctional envelope-type nano device (MEND) for efficient nucleic acid delivery. Here, we report on the development of an octaarigine (R8)-modified MEND encapsulating small interfering RNA (siRNA) with a tumor-specific, cleavable, polyethylene glycol (PEG)-lipid (PPD). We first determined the optimal concentration of R8 and pH-sensitive fusogenic peptide (GALA) on the lipid envelope of MEND (R8/GALA-MEND). Then, we examined the combination of optimized R8/GALA-MEND with a PEG-lipid. When a conventional PEG-lipid was used, the R8/GALA-MEND failed to knockdown expression of the target gene. On the other hand, PPD-modified R8/GALA-MEND exhibited efficient silencing activity to the level of the PEG-unmodified R8/GALA-MEND. In addition, we compared a R8/GALA-MEND with a MEND composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) that is a conventional cationic lipid used as a lipoplex component. The knockdown ability of the R8/GALA-MEND was much higher than that of the DOTAP-based MEND at the dose that is commonly employed in in vitro siRNA transfection. These results demonstrate that the R8/GALA-MEND is a promising delivery system for the transfer of siRNA to tumor cells.
- Pharmaceutical Society of Japanの論文
著者
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原島 秀吉
北大院・薬学研究科
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Akita Hidetaka
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Shim Chang
Faculty Of Pharmaceutical Sciences University Of Tokyo : (present Address) College Of Pharmacy Seoul
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HARASHIMA Hideyoshi
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
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Harashima Hideyoshi
Laboratory For Molecular Design Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokkaido Univers
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Akita Hidetaka
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
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Akita Hidetaka
Graduate School Of Pharmaceutical Sciences Hokkaido University
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Nagasaki Yukio
Tsukuba Res. Institure For Interdisciplinary Materials Sci. Univ. Of Tsukuba
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Sakurai Yu
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
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Hatakeyama Hiroto
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido Unive
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Oishi Motoi
Tsukuba Research Center for Interdisciplinary Material Science (TIMS), University of Tsukuba
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Futaki Shiro
Institute for Chemical Research, Kyoto University
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Hatakeyama Hiroto
Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Harashima Hideyoshi
Fac. Of Pharmaceutical Sciences Hokkaido Univ. Kita-12 Nishi-6 Kita-ku Sapporo 060-0812 Jpn
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Nagasaki Yukio
Tsukuba Research Center for Interdisciplinary Material Science (TIMS), University of Tsukuba
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Akita Hidetaka
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
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Sakurai Yu
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
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