Bioconjugated gold nanoparticles enhance siRNA delivery in prostate cancer cells

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Date
2019-05-17
Authors
Rahme, Kamil
Guo, Jianfeng
Holmes, Justin D.
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Springer
Published Version
10.1007/978-1-4939-9220-1_21
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Abstract
Here we describe a simple way to create a gold nanoparticle (AuNP)-based non-viral delivery system to deliver siRNA into prostate cancer cells. Therefore, positively charged polyethylenimine (PEI)-capped AuNPs were synthesized in water and further conjugated with the targeting ligand (folic acid) for folate receptors (AuNPs-PEI-FA). The AuNPs-PEI-FA could effectively complex small interfering RNA (siRNA) through electrostatic interaction. Flow cytometry displayed that AuNPs-PEI-FA could specifically deliver siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate-specific membrane antigen (PSMA) that exhibits a hydrolase enzymatic activity with a folate substrate. In contrast, internalization of siRNA into PC-3 cells, a prostate cancer cell line not expressing PSMA or folate receptors, was not achieved using AuNPs-PEI-FA.siRNA. Following endolysosomal escape, the AuNPs-PEI-FA-.siRNA formulation resulted in significant endogenous gene silencing when compared to the nontargeted formulation, suggesting the potential of AuNPs-PEI-FA for targeted delivery of therapeutic siRNAs in the treatment of prostate cancer.
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Keywords
Gold nanoparticles , Targeting ligands , Receptor-mediated internalization , Non-viral siRNA delivery , Prostate cancer , Gene therapy , ~Chemistry - Book Chapters~ , ~Tyndall National Institute - Book Chapters~
Citation
Rahme, K., Guo, J. and Holmes, J. D. (2019) 'Bioconjugated Gold Nanoparticles Enhance siRNA Delivery in Prostate Cancer Cells', in Dinesh Kumar, L. (ed.) RNA Interference and Cancer Therapy: Methods and Protocols. New York, NY: Springer New York, pp. 291-301. doi: 10.1007/978-1-4939-9220-1_21
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https://link.springer.com/protocol/10.1007%2F978-1-4939-9220-1_21
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https://hdl.handle.net/10468/7970
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School of Chemistry
Tyndall National Institute - Book Chapters
Copyright
© 2019 Springer. This is a post-peer-review, pre-copyedit version of a book chapter published in RNA Interference and Cancer Therapy Methods and Protocols; Methods in Molecular Biology book series (MIMB, volume 1974), The final authenticated version is available online at: http://dx.doi.org/10.1007/978-1-4939-9220-1_21