Skip to main content

Bioconjugated Gold Nanoparticles Enhance siRNA Delivery in Prostate Cancer Cells

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

This is a preview of subscription content, access via your institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-4939-9220-1_21
  • Chapter length: 11 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   109.00
Price excludes VAT (USA)
  • ISBN: 978-1-4939-9220-1
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   149.99
Price excludes VAT (USA)
Hardcover Book
USD   219.99
Price excludes VAT (USA)
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics. CA Cancer J Clin 65:5–29

    CrossRef  PubMed  Google Scholar 

  2. WKNg V, Berti R, Lesage F, Kakkar A (2013) Gold: a versatile tool for in vivo imaging. J Mater Chem B 1:9–25

    Google Scholar 

  3. Jain S, Hirst DG, O’Sullivan JM (2012) Gold nanoparticles as novel agents for cancer therapy. Br J Radiol 85:101–113

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  4. Fratoddi I, Venditti I, Cametti C, Russo MV (2014) Gold nanoparticles and gold nanoparticle-conjugates for delivery of therapeutic molecules. Progress and challenges. J Mater Chem B 2:4204–4220

    CAS  CrossRef  PubMed  Google Scholar 

  5. Guo J, Rahme K, Fitzgerald KA, Holmes JD, O’Driscoll CM (2015) Biomimetic gold nanocomplexes for gene knockdown: will gold deliver dividends for small interfering RNA nanomedicines? Nano Res 8:3111–3140

    CAS  CrossRef  Google Scholar 

  6. Wittrup A, Lieberman J (2015) Knocking down disease: a progress report on siRNA therapeutics. Nat Rev Genet 16:543–552

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  7. Fitzgerald KA, Evans JC, McCarthy J, Guo J, Prencipe M, Meghan K, Watson WR, O’Driscoll CM (2014) The role of transcription factors in prostate cancer and potential for future RNA interference therapy. Expert Opin Ther Targets 18:633–649

    CAS  CrossRef  PubMed  Google Scholar 

  8. Guo J, McKenna SL, O’Dwyer ME, Cahill MR, O’Driscoll CM (2015) RNA interference for multiple myeloma therapy: targeting signal transduction pathways. Expert Opin Ther Targets 20:107–121

    CrossRef  PubMed  Google Scholar 

  9. Strumberg D, Schultheis B, Traugott U, Vank C, Santel A, Keil O, Giese K, Kaufmann J, Drevs J (2012) Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors. Int J Clin Pharmacol Ther 50:76–78

    CAS  CrossRef  PubMed  Google Scholar 

  10. Tabernero J et al (2013) First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov 3:406–417

    CAS  CrossRef  PubMed  Google Scholar 

  11. Guo J, Cahill MR, McKenna SL, O’Driscoll CM (2014) Biomimetic nanoparticles for siRNA delivery in the treatment of leukaemia. Biotechnol Adv 32:1396–1409

    CAS  CrossRef  PubMed  Google Scholar 

  12. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108

    CAS  CrossRef  PubMed  Google Scholar 

  13. Van Steenis JH et al (2003) Preparation and characterization of folate-targeted PEG-coated pDMAEMA-based polyplexes. J Control Release 87:167–176

    CrossRef  PubMed  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Kamil Rahme or Jianfeng Guo .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

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

About this protocol

Verify currency and authenticity via CrossMark

Cite this protocol

Rahme, K., Guo, J., Holmes, J.D. (2019). Bioconjugated Gold Nanoparticles Enhance siRNA Delivery in Prostate Cancer Cells. In: Dinesh Kumar, L. (eds) RNA Interference and Cancer Therapy. Methods in Molecular Biology, vol 1974. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9220-1_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9220-1_21

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9219-5

  • Online ISBN: 978-1-4939-9220-1

  • eBook Packages: Springer Protocols