論文 - 詳細
| RRC ID | 37645 |
|---|---|
| 著者 | Hatakeyama H, Ito E, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H. |
| タイトル | A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. |
| ジャーナル | J Control Release |
| Abstract |
Previously, we developed a multifunctional envelope-type nano device (MEND) for efficient delivery of both pDNA and siRNA. Modification of a MEND with polyuethylene glycol, i.e., PEGylation, is a potential strategy for in vivo delivery of MENDs to tumor tissue. However, PEGylation also inhibits both uptake and endosomal escape of MENDs. To overcome these limitations, we developed a PEG-peptide-DOPE (PPD) that can be cleaved in a matrix metalloproteinase (MMP)-rich environment. In this study, to further improve the silencing activity of encapsulated siRNA, we modified the PPD-MEND with a pH-sensitive fusogenic GALA peptide (GALA/PPD-MEND). First, we determined the GALA and PPD content that would optimize the synergistic functions of GALA and PPD. The most efficient gene silencing activity was achieved when GALA and either conventional PEG-lipid or PPD were used to modify the MEND at a molar ratio of 1:1. In this case, the silencing activity was comparable to that achieved when using a MEND that had not been modified with PEG (unmodified MEND). Furthermore, in vivo topical administration revealed that optimized PPD/GALA-MENDa resulted in more efficient gene silencing compared with unmodified MENDs. Collectively, data demonstrate that introduction of both of a pH-sensitive fusogenic GALA peptide and PPD into the MEND facilitates nanoparticle endosomal escape, thereby enhancing the efficiency of siRNA delivery and gene silencing. |
| 巻・号 | 139(2) |
| ページ | 127-32 |
| 公開日 | 2009-10-15 |
| DOI | 10.1016/j.jconrel.2009.06.008 |
| PII | S0168-3659(09)00418-0 |
| PMID | 19540888 |
| MeSH | Animals Gene Silencing HeLa Cells Humans Hydrogen-Ion Concentration Male Mice Mice, Inbred BALB C Nanoparticles / chemistry* Neoplasms / therapy Peptides / chemistry* Phosphatidylethanolamines / chemistry* Polyethylene Glycols / chemistry* RNA, Small Interfering / administration & dosage* RNA, Small Interfering / therapeutic use |
| IF | 7.727 |
| 引用数 | 178 |
| WOS 分野 | PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HT1080(RCB1956) |