Projects per year
Abstract
Pancreatic cancer is a devastating disease with a dismal prognosis. Short-interfering RNA (siRNA)-based therapeutics hold promise for the treatment of cancer. However, development of efficient and safe delivery vehicles for siRNA remains a challenge. Here, we describe the synthesis and physicochemical characterization of star polymers (star 1, star 2, star 3) using reversible addition-fragmentation chain transfer polymerization (RAFT) for the delivery of siRNA to pancreatic cancer cells. These star polymers were designed to contain different lengths of cationic poly(dimethylaminoethyl methacrylate) (PDMAEMA) side-arms and varied amounts of poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA). We showed that star-POEGMA polymers could readily self-assemble with siRNA to form nanoparticles. The star-POEGMA polymers were nontoxic to normal cells and delivered siRNA with high efficiency to pancreatic cancer cells to silence a gene (TUBB3/βIII-tubulin) which is currently undruggable using chemical agents, and is involved in regulating tumor growth and metastases. Notably, systemic administration of star-POEGMA-siRNA resulted in high accumulation of siRNA to orthotopic pancreatic tumors in mice and silenced βIII-tubulin expression by 80% at the gene and protein levels in pancreatic tumors. Together, these novel findings provide strong rationale for the use of star-POEGMA polymers as delivery vehicles for siRNA to pancreatic tumors.
| Original language | English |
|---|---|
| Pages (from-to) | 2337-2351 |
| Number of pages | 15 |
| Journal | Biomacromolecules |
| Volume | 17 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 11 Jul 2016 |
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Projects
- 2 Finished
-
Macromolecular design for bio-imaging and targeted delivery
Davis, T. (Primary Chief Investigator (PCI))
Australian Research Council (ARC), Monash University
1/07/14 → 31/12/19
Project: Research
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ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
Davis, T. (Primary Chief Investigator (PCI)), Boyd, B. (Chief Investigator (CI)), Bunnett, N. (Chief Investigator (CI)), Porter, C. (Chief Investigator (CI)), Caruso, F. (Chief Investigator (CI)), Kent, S. (Chief Investigator (CI)), Thordarson, P. (Chief Investigator (CI)), Kearnes, M. (Chief Investigator (CI)), Gooding, J. (Chief Investigator (CI)), Kavallaris, M. (Chief Investigator (CI)), Thurecht, K. (Chief Investigator (CI)), Whittaker, A. K. (Chief Investigator (CI)), Parton, R. (Chief Investigator (CI)), Corrie, S. R. (Chief Investigator (CI)), Johnston, A. (Chief Investigator (CI)), McGhee, J. (Chief Investigator (CI)), Greguric, I. D. (Partner Investigator (PI)), Stevens, M. M. (Partner Investigator (PI)), Lewis, J. S. (Partner Investigator (PI)), Lee, D. S. (Partner Investigator (PI)), Alexander, C. (Partner Investigator (PI)), Dawson, K. (Partner Investigator (PI)), Hawker, C. (Partner Investigator (PI)), Haddleton, D. (Partner Investigator (PI)), Thierry, B. (Chief Investigator (CI)), Prestidge, C. A. (Chief Investigator (CI)), Meyer, A. (Project Manager), Jones-Jayasinghe, N. (Project Manager), Voelcker, N. (Chief Investigator (CI)), Nann, T. (Chief Investigator (CI)) & McLean, K. (Partner Investigator (PI))
Australian Research Council (ARC), Monash University, University of Melbourne, University of New South Wales (UNSW), University of Queensland , University of South Australia, Monash University – Internal Faculty Contribution, University of Wisconsin Madison, Memorial Sloan Kettering Cancer Center, University of California System, University College Dublin, Imperial College London, University of Warwick, Sungkyunkwan University, Australian Nuclear Science and Technology Organisation (ANSTO) , University of Nottingham
30/06/14 → 29/06/21
Project: Research