論文 - 詳細
| RRC ID | 63448 |
|---|---|
| 著者 | Yamada Y, Furukawa R, Harashima H. |
| タイトル | A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting. |
| ジャーナル | J Pharm Sci |
| Abstract |
It has been reported that the use of mitochondrial RNA aptamers including RNase P (RP) results in the selective mitochondrial delivery of endogenous and exogenous RNAs. The issue of whether these aptamers would be useful ligands for the mitochondrial targeting of a nanoparticle has not been demonstrated to date because nanocarriers modified with these RNA aptamers are insufficiently internalized by cells. We report here on the development of a dual-ligand liposomal system composed of octaarginine (R8), a device that enhances cellular uptake, and an RP aptamer for mitochondrial targeting to permit a nanocarrier to be efficiently delivered to mitochondria. Surprisingly, the cellular uptake of the R8-modified nanocarrier was facilitated by modification with an RP aptamer. The optimal composition of a nanocarrier needed for efficient cellular uptake and mitochondrial targeting was determined. In a confocal laser scanning microscopy analysis, the dual-ligand-modified nanocarrier was found to result in effective mitochondrial targeting through an ATP-dependent pathway and was much more effective than a single-ligand R8-modified nanocarrier. This is the first report of the regulation of intracellular trafficking by a mitochondrial RNA aptamer-modified nanocarrier system. |
| 巻・号 | 105(5) |
| ページ | 1705-1713 |
| 公開日 | 2016-5-1 |
| DOI | 10.1016/j.xphs.2016.03.002 |
| PII | S0022-3549(16)00402-0 |
| PMID | 27056631 |
| MeSH | Aptamers, Nucleotide / administration & dosage Aptamers, Nucleotide / metabolism* Cell-Penetrating Peptides / administration & dosage Cell-Penetrating Peptides / metabolism* Drug Carriers / administration & dosage Drug Carriers / metabolism Drug Delivery Systems / methods* Drug Synergism HeLa Cells Humans Intracellular Fluid / drug effects Intracellular Fluid / metabolism* Ligands Liposomes Mitochondria / drug effects Mitochondria / metabolism* RNA / administration & dosage RNA / metabolism* RNA, Mitochondrial |
| IF | 2.997 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa |