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Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System
| Title: | Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System |
| Authors: | Sakurai, Yu Browse this author | | Hatakeyama, Hiroto Browse this author | | Akita, Hidetaka Browse this author | | Oishi, Motoi Browse this author | | Nagasaki, Yukio Browse this author | | Futaki, Shiro Browse this author | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | non-viral delivery system | | stearyl octaarginine | | cancer gene therapy | | multifunctional envelope-type nano device | | pH-sensitive furogenic peptide |
| Issue Date: | May-2009 |
| Publisher: | Pharmaceutical Society of Japan |
| Journal Title: | Biological & Pharmaceutical Bulletin |
| Volume: | 32 |
| Issue: | 5 |
| Start Page: | 928 |
| End Page: | 932 |
| Publisher DOI: | 10.1248/bpb.32.928 |
| Abstract: | 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/38623 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 原島 秀吉
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