ALPPL2 Aptamer-Mediated Targeted Delivery of 5-Fluoro-2'-Deoxyuridine to Pancreatic Cancer.

Nucleic Acid Ther

1 Global Research Laboratory of RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon, Korea.

Published: August 2015

Nucleoside analogues are the most promising drugs for the treatment of pancreatic cancer to date. However, their use is often limited due to toxic side effects. Aptamer-mediated targeted delivery of these drugs to cancer cells could maximize their effectiveness and concomitantly minimize the toxic side effects by reducing uptake into normal cells. Previously, we identified a pancreatic cancer-specific, nuclease-resistant RNA aptamer, SQ2, which binds to alkaline phosphatase placental-like 2 (ALPPL2), a putative biomarker for pancreatic cancer. In this study, we demonstrate that the aptamer can be internalized into pancreatic cancer cells and can thus be used for the targeted delivery of therapeutics. Using the aptamer as a ligand, we established that glycophosphatidylinositol-anchored ALPPL2 is internalized by the cells through clathrin-independent and caveolae-dependent or dynamin-mediated cell-type-dependent pathways. Finally, we show that SQ2 can deliver nucleoside drug 5-fluoro-2'-deoxyuridine specifically to ALPPL2-expressing pancreatic cancer cells, inhibiting cell proliferation.

Download full-text PDF

Source
http://dx.doi.org/10.1089/nat.2014.0516DOI Listing

Publication Analysis

Top Keywords

pancreatic cancer
20
targeted delivery
12
cancer cells
12
aptamer-mediated targeted
8
toxic side
8
side effects
8
pancreatic
6
cancer
6
cells
5
alppl2 aptamer-mediated
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!