|
Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
RNAi-mediated gene knockdown and anti-angiogenic therapy of RCCs using a cyclic RGD-modified liposomal-siRNA system
| Title: | RNAi-mediated gene knockdown and anti-angiogenic therapy of RCCs using a cyclic RGD-modified liposomal-siRNA system |
| Authors: | Sakurai, Yu Browse this author | | Hatakeyama, Hiroto Browse this author →KAKEN DB | | Sato, Yusuke Browse this author | | Hyodo, Mamoru Browse this author →KAKEN DB | | Akita, Hidetaka Browse this author →KAKEN DB | | Ohga, Noritaka Browse this author →KAKEN DB | | Hida, Kyoko Browse this author →KAKEN DB | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | siRNA | | Liposome | | Anti-angiogenic therapy | | Cyclic RGD | | Active targeting |
| Issue Date: | 10-Jan-2014 |
| Publisher: | Elsevier science bv |
| Journal Title: | Journal of controlled release |
| Volume: | 173 |
| Start Page: | 110 |
| End Page: | 118 |
| Publisher DOI: | 10.1016/j.jconrel.2013.10.003 |
| PMID: | 24120854 |
| Abstract: | Angiogenesis is one of crucial processes associated with tumor growth and development, and consequently a prime target for cancer therapy. Although tumor endothelial cells (TECs) play a key role in pathological angiogenesis, investigating phenotypical changes in neovessels when a gene expression in TEC is suppressed is a difficult task. Small interfering RNA (siRNA) represents a potential agent due to its ability to silence a gene of interest. We previously developed a system for in vivo siRNA delivery to cancer cells that involves a liposomal-delivery system, a MEND that contains a unique pH-sensitive cationic lipid, YSK05 (YSK-MEND). In the present study, we report on the development of a system that permits the delivery of siRNA to TECs by combining the YSK-MEND and a ligand that is specific to TECs. Cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) is a well-known ligand to alpha(V)beta(3) integrin, which is selectively expressed at high levels in TECs. We incorporated cRGD into the YSK-MEND (RGD-MEND) to achieve an efficient gene silencing in TECs. Quantitative RT-PCR and the 5' rapid amplification of cDNA ends PCR indicated that the intravenous injection of RGD-MEND at a dose of 4.0 mg/kg induced a significant RNAi-mediated gene reduction in TEC but not in endothelial cells of other organs. Finally, we evaluated the therapeutic potency of the RGD-MEND encapsulating siRNA against vascular endothelial growth factor receptor 2. A substantial delay in tumor growth was observed after three sequential RGD-MEND injections on alternate days. In conclusion, the RGD-MEND represents a new approach for the characterization of TECs and for us in anti-angiogenic therapy. (C) 2013 Elsevier B.V. All rights reserved. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/57252 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 櫻井 遊
|
