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A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo
| Title: | A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo |
| Authors: | Sato, Yusuke Browse this author | | Hatakeyama, Hiroto Browse this author →KAKEN DB | | Sakurai, Yu Browse this author | | Hyodo, Mamoru Browse this author | | Akita, Hidetaka Browse this author →KAKEN DB | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | Multifunctional envelope-type nano device (MEND) | | siRNA delivery | | pH-sensitive cationic lipid | | Intracellular trafficking | | Endosomal escape |
| Issue Date: | 10-Nov-2012 |
| Publisher: | Elsevier B.V. |
| Journal Title: | Journal of Controlled Release |
| Volume: | 163 |
| Issue: | 3 |
| Start Page: | 267 |
| End Page: | 276 |
| Publisher DOI: | 10.1016/j.jconrel.2012.09.009 |
| PMID: | 23000694 |
| Abstract: | Modification of liposomal siRNA carriers with polyethylene glycol, i.e., PEGylation, is a generally accepted strategy for achieving in vivo stability and delivery to tumor tissue. However, PEGylation significantly inhibits both cellular uptake and the endosomal escape process of the carriers. In a previous study, we reported on the development of a multifunctional envelope-type nano device (MEND) for siRNA delivery and peptide-based functional devices for overcoming the limitations and succeeded in the efficient delivery of siRNA to tumors. In this study, we synthesized a pH-sensitive cationic lipid, YSK05, to overcome the limitations. The YSK05-MEND had a higher ability for endosomal escape than other MENDs containing conventional cationic lipids. The PEGylated YSK05-MEND induced efficient gene silencing and overcame the limitations followed by optimization of the lipid composition. Furthermore, the intratumoral administration of the YSK05-MEND resulted in a more efficient gene silencing compared with MENDs containing conventional cationic lipids. Collectively, these data confirm that YSK05 facilitates the endosomal escape of the MEND and thereby enhances the efficacy of siRNA delivery into cytosol and gene silencing. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/51165 |
| 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: 畠山 浩人
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