Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/29306
Title: Biodegradable nanoparticle-mediated K-ras down regulation for pancreatic cancer gene therapy
Authors: Yang, C
Hu, R
Anderson, T
Wang, Y
Lin, G
Law, WC
Lin, WJ
Nguyen, QT
Toh, HT
Yoon, HS
Chen, CK
Yong, KT
Issue Date: 2015
Publisher: Royal Society of Chemistry
Source: Journal of materials chemistry B, 2015, v. 3, no. 10, p. 2163-2172 How to cite?
Journal: Journal of materials chemistry B 
Abstract: RNA interference (RNAi) targeting the K-ras oncogene mutation in pancreatic cancer mediated by small interfering RNA (siRNA) transfection is a very promising treatment. However, the rapid degradation and negative charge of naked siRNAs restrict their direct delivery into cells. In this contribution, we propose a safe and effective transmembrane transport nanocarrier formulation based on a newly developed biodegradable charged polyester-based vector (BCPV) for K-ras siRNA delivery into pancreatic cancer cells. Our results have shown that these biodegradable and biocompatible vectors are able to transfect siRNAs targeting mutant K-ras into MiaPaCa-2 cells with high transfection and knockdown efficiency. More importantly, the RNAi process initiated a cascade gene regulation of the downstream proteins of K-ras associated with cell proliferation, migration, invasion and apoptosis. We observed that after the mutant K-ras siRNA transfection, the growth, migration and invasion of the MiaPaCa-2 cells were significantly reduced; also, the apoptosis of the pancreatic cancer cells was promoted. Although in vivo testing data are limited, we propose that the BCPV based nanoparticle formulation could be a promising candidate as non-viral vectors for gene therapy in clinical settings.
URI: http://hdl.handle.net/10397/29306
ISSN: 2050-750X
EISSN: 2050-7518
DOI: 10.1039/c4tb01623h
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