Bioconjugated gold nanoparticles enhance cellular uptake: a proof of concept study for siRNA delivery in prostate cancer cells
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Date
2016-05-14
Authors
Guo, Jianfeng
O'Driscoll, Caitríona M.
Holmes, Justin D.
Rahme, Kamil
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Published Version
Abstract
The chemistry of gold nanoparticles (AuNPs) facilitates surface modifications and thus these bioengineered NPs have been investigated as a means of delivering a variety of therapeutic cargos to treat cancer. In this study we have developed AuNPs conjugated with targeting ligands to enhance cell-specific uptake in prostate cancer cells, with a purpose of providing efficient non-viral gene delivery systems in the treatment of prostate cancer. As a consequence, two novel AuNPs were synthesised namely AuNPs-PEG-Tf (negatively charged AuNPs with the transferrin targeting ligands) and AuNPs-PEI-FA (positively charged AuNPs with the folate-receptor targeting ligands). Both bioconjugated AuNPs demonstrated low cytotoxicity in prostate cancer cells. The attachment of the targeting ligand Tf to AuNPs successfully achieved receptor-mediated cellular uptake in PC-3 cells, a prostate cancer cell line highly expressing Tf receptors. The AuNPs-PEI-FA effectively complexed small interfering RNA (siRNA) through electrostatic interaction. At the cellular level the AuNPs-PEI-FA specifically delivered siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate specific membrane antigen (PSMA, exhibits a hydrolase enzymic activity with a folate substrate). Following endolysosomal escape the AuNPs-PEI-FA.siRNA formulation produced enhanced endogenous gene silencing compared to the non-targeted formulation. Our results suggest both formulations have potential as non-viral gene delivery vectors in the treatment of prostate cancer.
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Keywords
Gold nanoparticles , Targeting ligands , Receptor-mediated internalisation , Non-viral siRNA delivery , Prostate cancer gene therapy
Citation
Guo, J., O’Driscoll, C. M., Holmes, J. D. and Rahme, K. (2016) 'Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells', International Journal of Pharmaceutics, 509(1), pp. 16-27. doi: 10.1016/j.ijpharm.2016.05.027