RRC ID 37873
著者 Sakurai Y, Hatakeyama H, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H.
タイトル Efficient short interference RNA delivery to tumor cells using a combination of octaarginine, GALA and tumor-specific, cleavable polyethylene glycol system.
ジャーナル Biol Pharm Bull
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.
巻・号 32(5)
ページ 928-32
公開日 2009-5-1
DOI 10.1248/bpb.32.928
PII JST.JSTAGE/bpb/32.928
PMID 19420766
MeSH Drug Delivery Systems / methods* Fatty Acids, Monounsaturated / chemistry Gene Silencing / drug effects Gene Transfer Techniques* HeLa Cells Humans Luciferases / genetics Nanoparticles / chemistry Oligopeptides / chemistry* Peptides / chemistry* Polyethylene Glycols / chemistry* Quaternary Ammonium Compounds / chemistry RNA, Small Interfering / administration & dosage* Transfection
IF 1.863
引用数 35
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 HeLa(RCB0007)