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Construction of an Aptamer Modified Liposomal System Targeted to Tumor Endothelial Cells

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Title: Construction of an Aptamer Modified Liposomal System Targeted to 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
Ohga, Noritaka Browse this author →KAKEN DB
Hida, Kyoko Browse this author →KAKEN DB
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: aptamer based liposome
targeted drug delivery
tumor endothelial cell
heat shock protein 70 (HSP70)
cell-based systematic evolution of ligands by exponential enrichment
Issue Date: Nov-2014
Publisher: The Pharmaceutical Society of Japan
Journal Title: Biological & pharmaceutical bulletin
Volume: 37
Issue: 11
Start Page: 1742
End Page: 1749
Publisher DOI: 10.1248/bpb.b14-00338
PMID: 25366480
Abstract: We describe herein the development of a high affinity and specific DNA aptamer as a new ligand for use in liposomal nanoparticles to target cultured mouse tumor endothelial cells (mTECs). Active targeted nanotechnology based drug delivery systems are currently of great interest, due to their potential for reducing side effects and facilitating the delivery of cytotoxic drugs or genes in a site specific manner. In this study, we report on a promising aptamer candidate AraHH036 that shows selective binding towards mTECs. The aptamer does not bind to normal cells, normal endothelial cells or tumor cells. Therefore, we synthesized an aptamer-polyethylene glycol (PEG) lipid conjugate and prepared aptamer based liposomes (ALPs) by the standard lipid hydration method. First, we quantified the higher capacity of ALPs to internalize into mTECs by incubating ALPs containing 1 mol%, 5 mol% and 10 mol% aptamer of total lipids and compared the results to those for unmodified PEGylated liposomes (PLPs). A confocal laser scanning microscope (CLSM) uptake study indicated that the ALPs were taken up more efficiently than PLPs. The measured K-d value of the ALPs was 142 nM. An intracellular trafficking study confirmed that most of the rhodamine labeled ALPs were taken up and co-localized with the green lysotracker, thus confirming that they were located in lysosomes. Finally, using an aptamer based proteomics approach, the molecular target protein of the aptamer was identified as heat shock protein 70 (HSP70). The results suggest that these ALPs offer promise as a new carrier molecule for delivering anti-angiogenesis drugs to tumor vasculature.
Type: article
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: 原島 秀吉

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