Grant: Operating Grant

Bladder cancer is the fifth most common cancer in Canada and the incidence is increasing. Superficial disease is treated by surgical removal of tumors and the intravesical instillation of chemotherapy agents, usually mitomycin C, directly into the bladder via a catheter. However, the highly impermeable barrier presented by the superficial umbrella cells of the bladder wall seriously limit drug uptake and effectiveness of intravesical chemotherapy and patients require life-long surveillance, usually with repeated interventions. New therapeutic approaches are urgently needed. We have developed tiny, spherical nano-sized particles that are very highly branched and possess a core that can carry a payload of docetaxel and a surface that can be modified with positively charged amine groups. These nanoparticles show markedly superior bladder tissue drug levels and efficacy in a mouse model of superficial bladder cancer and we believe this may be explained by the amine coated nanoparticles causing shedding of the surface barrier cells. We also found that, following removal of the nanoparticles and washing of the bladder tissue, the superficial cell layer was regenerated extremely rapidly, within hours. The goal of this translational research is to develop these unique drug nanoparticles for potential treatment of patients receiving intravesical chemotherapy after surgical resection of tumors. The objectives are to investigate the processes leading to superficial cell shedding and recovery, to determine the uptake and distribution of the drug and nanoparticles in bladder and tumor tissue and to evaluate the efficacy and toxicity of the drug loaded nanoparticles in mouse models of superficial bladder cancer.