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

Ara, Mst Naznin; Matsuda, Takashi; Hyodo, Mamoru; Sakurai, Yu; Hatakeyama, Hiroto; Ohga, Noritaka; Hida, Kyoko; Harashima, Hideyoshi

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

Ara, Mst Naznin; Matsuda, Takashi; Hyodo, Mamoru et al.

Biomaterials, 2014, 35(25), 7110-7120

Permalink : https://hdl.handle.net/2115/57445

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アクセス権	open access
URI	https://hdl.handle.net/2115/57445
タイトル	An aptamer ligand based liposomal nanocarrier system that targets tumor endothelial cells
著者	Ara, Mst Naznin ; Matsuda, Takashi ; Hyodo, Mamoru ; Sakurai, Yu ; Hatakeyama, Hiroto ; Ohga, Noritaka ; Hida, Kyoko ; Harashima, Hideyoshi
著者名 Ara, Mst Naznin
著者名 Matsuda, Takashi
e-Rad_Researcher 30548186 著者名 Hyodo, Mamoru
著者名 Sakurai, Yu
e-Rad_Researcher 70504786 著者名 Hatakeyama, Hiroto
e-Rad_Researcher 40548202 著者名 Ohga, Noritaka
e-Rad_Researcher 40399952 著者名 Hida, Kyoko
e-Rad_Researcher 00183567 著者名 Harashima, Hideyoshi
言語	英語
キーワード	Targeted delivery
	Aptamer-liposomes
	Endocytosis
	Intracellular uptake
	Tumor endothelial cells
発行日	2014-08
出版者	Elsevier
収録物名	Biomaterials
巻(号)	35(25)
ページ	7110-7120
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0142-9612
関連情報	PMID 24875764
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.biomaterials.2014.04.087