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Bioconjugated Gold Nanoparticles Enhance siRNA Delivery in Prostate Cancer Cells

  • Kamil RahmeEmail author
  • Jianfeng GuoEmail author
  • Justin D. Holmes
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1974)

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.

Keywords

Gold nanoparticles Targeting ligands Receptor-mediated internalization Non-viral siRNA delivery Prostate cancer Gene therapy 

Notes

Acknowledgments

We acknowledge the financial support from Science Foundation Ireland and AMBER (Grant 12/RC/2278); the Irish Research Council, for a Government of Ireland Postdoctoral Fellowship (GOIPD/2013/150) and the Outstanding Youth Foundation from the Department of Science and Technology, Jilin Province (Project Number: 20170520046JH), to Jianfeng Guo; and the National Council for Scientific Research Lebanon (CNRS-L-GRP2015).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Sciences, Faculty of Natural and Applied SciencesNotre Dame University-LouaizeZouk MosbehLebanon
  2. 2.Materials Chemistry and Analysis Group, School of Chemistry, Tyndall National InstituteUniversity College CorkCorkIreland
  3. 3.School of Pharmaceutical SciencesJilin UniversityChangchunChina
  4. 4.Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN)Trinity College DublinDublin 2Ireland

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