Reference - Detail
| RRC ID | 37645 |
|---|---|
| Author | Hatakeyama H, Ito E, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H. |
| Title | A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. |
| Journal | 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. |
| Volume | 139(2) |
| Pages | 127-32 |
| Published | 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 |
| Times Cited | 178 |
| WOS Category | PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HT1080(RCB1956) |