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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Publisher
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
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
URI
https://hdl.handle.net/10468/7970
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Chemistry - Book Chapters
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