|
Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
An aptamer ligand based liposomal nanocarrier system that targets tumor endothelial cells
| Title: | An aptamer ligand based liposomal nanocarrier system that targets tumor endothelial cells |
| Authors: | Ara, Mst Naznin Browse this author | | Matsuda, Takashi Browse this author | | Hyodo, Mamoru Browse this author →KAKEN DB | | Sakurai, Yu Browse this author | | Hatakeyama, Hiroto 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: | Targeted delivery | | Aptamer-liposomes | | Endocytosis | | Intracellular uptake | | Tumor endothelial cells |
| Issue Date: | Aug-2014 |
| Publisher: | Elsevier |
| Journal Title: | Biomaterials |
| Volume: | 35 |
| Issue: | 25 |
| Start Page: | 7110 |
| End Page: | 7120 |
| Publisher DOI: | 10.1016/j.biomaterials.2014.04.087 |
| PMID: | 24875764 |
| Abstract: | The objective of this study was to construct our recently developed aptamer-modified targeted liposome nano-carrier (Apt-PEG-LPs) system to target primary cultured mouse tumor endothelial cells (mTEC), both in vitro and in vivo. We first synthesized an aptamer-polyethylene glycol 2000-distearoyl phosphoethanolamine (Apt-PEG(2000)-DSPE). The conjugation of the Apt-PEG(2000)-DSPE was confirmed by MALDI-TOF mass spectroscopy. A lipid hydration method was used to prepare Apt-PEG-LPs, in which the outer surface of the PEG-spacer was decorated with the aptamer. Apt-PEG-LPs were significantly taken up by mTECs. Cellular uptake capacity was observed both quantitatively and qualitatively using spectrofluorometry, and confocal laser scanning microscopy (CLSM), respectively. In examining the extent of localization of aptamer-modified liposomes that entered the cells, approximately 39% of the Apt-PEG-LPs were not co-localized with lysotracker, indicating that they had escaped from endosomes. The uptake route involved a receptor mediated pathway, followed by clathrin mediated endocytosis. This Apt-PEG-LP was also applied for in vivo research whether this system could target tumor endothelial cells. Apt-PEG-LP and PEG(5000)-DSPE modified Apt-PEG-LP (Apt/PEG(5000)-LP) were investigated by human renal cell carcinoma (OS-RC-2 cells) inoculating mice using CLSM. Apt-PEG-LP and Apt/PEG(5000)-LP showed higher accumulation on tumor vasculature compared to PEG-LP and the co-localization efficacy of Apt-PEG-LP and Apt/PEG(5000)-LP on TEC were quantified 16% and 25% respectively, which was also better than PEG-LP (3%). The findings suggest that this system is considerable promise for targeting tumor endothelial cells to deliver drugs or genes in vitro and in vivo. (C) 2014 Elsevier Ltd. All rights reserved. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/57445 |
| 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
|
