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An aptamer ligand based liposomal nanocarrier system that targets tumor endothelial cells

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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

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