Research: 2017 – Grand River (Fleck)

Project Title:
Gold nanoparticles functionalized with plant-extract for targeted treatment of canine prostate cancer
Investigators:
Mr. Andre Fleck, MSc., MCCPM, Medical Physicist, Medical Physics Department, Grand River Cancer Centre;
Dr. Ernest Osei, Director Medical Physics Department, Grand River Cancer Center;
Dr. Johnson Darko, Medical Physics Department, Grand River Cancer Center;
Dr. Pierre Fortin, Department of Medical Oncology, Grand River Cancer Center;
Dr. Shawn Wettig, Associate Professor, School of Pharmacy, University of Waterloo;
Dr. Anthony Mutsaers, Associate Professor, Ontario Veterinary College, University of Guelph; Dr. Stephanie Nykamp, Associate Dean, Clinical Program, Ontario Veterinary College, University of Guelph;
Dr. Michelle Oblack, Assistant Professor, Ontario Veterinary College, University of Guelph
Lead Investigator Bio:
I am a Medical Physicist at Grand River Regional Centre. I received my B.Sc. from the University of Waterloo in Physics, my M.Sc. from the University of Regina in Subatomic Physics, and was working towards my Ph.D. at the University of Waterloo when I accepted the first medical physics residency at Grand River Hospital. I received my National Certification (Canadian College of Physicists in Medicine) in 2012.
Project Abstract:
Prostate cancer is the third leading cause of death from cancer in men in Canada. The overall goal of our research is to provide an effective treatment option and improve the quality of life of prostate cancer patients. As a step towards this goal, we aim to translate our findings from cell-culture and toxicity studies in small animals (mice) to clinical studies in canine patients suffering from naturally acquired prostate cancer. Previous funding from RFD has enabled us to accomplished the cell-culture and toxities studies in mice. Our next step before any human trial is to complete clinical trials in canine dogs. Dogs serve as excellent translational model for prostate cancer research since they too develop spontaneous prostate cancer similar to that observed in men. In place of the typical radiotherapy options that can be highly invasive with long recovery time or side effects and require many hospital visits, this research envisions a single injection of gold nanoparticles, coated with plant extract, into the prostate. Once in target, the nanoparticles deliver their therapeutic effects via the anti-cancer properties of the coating, radio-sensitization, imaging enhancement and the enhancement of externally delivered radiation dose. This multimodal-nanoparticle therapy potentially offers a reduced treatment burden while at the same time promising higher cure and lower complication rates. This combined and targeted treatment could change all aspects of managing prostate cancer.
Scientific Abstract:
Gold nanoparticles functionalized with plant extract (epigallocatechin gallate or curcumin), and delivered to the prostate through minimally invasive prostatic artery embolization technique can facilitate combined modality treatments for prostate cancer. Gold nanoparticles functionalized with epigallocatechin-gallate, and curcumin have demonstrated efficacy in the treatment of prostate cancer. We have synthesized and characterized epigallocatechin-gallate/curcumin functionalized gold nanoparticles. We propose to introduce these nanoparticles to the target prostate using a single injection through the prostatic arteries. The diffusion over time of the nanoparticles will be monitored with radiographs and computed tomography imaging, and controlled with embolization. Once bound to the target through the affinity of epigallocatechin-gallate to the overexpressed receptors (Laminin67R) of prostate cancer cells, the gold nanoparticles deliver therapeutic effects through the chemopreventative properties of epigallocatechin gallate and curcumin, the radiosensitization of the cancer cells through modification of the cell cycle, the enhancement of dose from external beams, and the enhancement of tumour imaging. This research has the potential to offer an alternative treatment option to current forms of radiotherapy, both external beam and brachytherapy, with a single minimally-invasive combined-modality treatment delivered in as short as just a single day hospital visit.
Impact on prostate cancer patients:
The outcome of this project will increase our understanding of the potential of gold nanoparticles as a treatment in combating prostate cancer. This has the potentially to dramatically change all current methods of treating prostate cancer and improve the survival and quality of life of prostate cancer patients. The eventual translation from canine to human would not only have a dramatic improvement in the quality of life of prostate cancer patients but also have a significant economic impact on the Canadian healthcare system. This combined modality nanoparticle therapy offers significant reduction of treatment burden while at the same time promising higher cure and lower complication rates.