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The Use of Star Polymer Nanoparticles for the Delivery of siRNA to Mouse Orthotopic Pancreatic Tumor Models

  • Joshua A. McCarroll
  • George Sharbeen
  • Maria Kavallaris
  • Phoebe A. PhillipsEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1974)

Abstract

Pancreatic cancer is a lethal malignancy which is refractory to most chemotherapy drugs. Recent landmark studies have shed new light on the complex genetic heterogeneity of pancreatic cancer and provide an opportunity to utilize “precision-based medicines” to target genes based on the genetic profile of an individual’s tumor to increase the efficiency of chemotherapy and decrease tumor growth and metastases. Gene-silencing drugs in the form of short-interfering RNA (siRNA) have the potential to play an important role in precision medicine for pancreatic cancer by silencing the expression of genes including those considered difficult to inhibit (undruggable) using chemical agents. However, before siRNA can reach its clinical potential a delivery vehicle is needed to carry siRNA across the cell membrane and into the cytoplasm of the cell. Herein, we detail the methods required to use star polymer nanoparticles to deliver siRNA to pancreatic tumors in an orthotopic pancreatic cancer mouse model to silence the expression of an “undruggable” gene (βIII-tubulin) that regulates pancreatic cancer growth and chemosensitivity.

Keywords

Pancreatic cancer Nanoparticles Short-interfering RNA (siRNA) Star polymers 

Notes

Acknowledgments

This work was supported by grants from the National Health and Medical Research Council (NHMRC; P. A. Phillips, J. McCarroll, M. Kavallaris; APP1024895), Cancer Council New South Wales (P. A. Phillips, J. McCarroll, M. Kavallaris), Cure Cancer Australia Foundation Grant (P. A. Phillips), Cancer Institute NSW Fellowship (J. McCarroll, G. Sharbeen), NHMRC CDF Fellowship (P. A. Phillips, APP1024896). M. Kavallaris is also supported by funding from National Health and Medical Research Council (NHMRC) Program Grant (APP1091261), Cancer Council NSW Program Grant (PG16-01), Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (project number CE140100036) and an NHMRC Principal Research Fellowship (APP1119152). Joshua A. McCarroll and George Sharbeen contributed equally to this work.Conflict of interest disclosure: The authors declare no competing financial interest.

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Copyright information

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

Authors and Affiliations

  • Joshua A. McCarroll
    • 1
    • 2
  • George Sharbeen
    • 3
  • Maria Kavallaris
    • 1
    • 2
  • Phoebe A. Phillips
    • 2
    • 3
    Email author
  1. 1.Tumour Biology and Targeting Program, Lowy Cancer Research Centre, Children’s Cancer InstituteUNSW SydneySydneyAustralia
  2. 2.Australian Centre for Nanomedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and TechnologyUNSW SydneySydneyAustralia
  3. 3.Pancreatic Cancer Translational Research Group, Lowy Cancer Research Centre, School of Medical SciencesUNSW SydneySydneyAustralia

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