Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Many attempts have been made to modify the distribution of chemotherapy drugs within the body in order to concentrate their activity within the tumour. An effective strategy has been to sequester the drug in a non-reactive carrier which then selectively accumulates in the tumour, degrades, and releases the drug. Liposomes, a non-reactive carrier, have found success in this regard; they have been shown to change the drug's distribution, reduce systemic toxicities, and increase drug concentrations at the tumour. Attempts have been made to further improve the drug accumulation at the tumour site or to increase the rate of liposome release relative to normal tissue, but limited success has been achieved. Recently, liposomes have been designed with the possibility for triggered release. In this case, an external source of energy is applied to the disease site to degrade liposomes designed with a vulnerability that is susceptible to exposure by external energy. The degraded liposomes subsequently release their drug only at the disease site. We hypothesize that by focusing the trigger (X-rays) on the disease site, only hybrid liposomes (such as, liposomes attached to gold nanoparticles, which are known to enhance X-rays) present in the energy field will release their drug contents and, thus, drug release will be controlled in a temporal and spatial manner. The following specific aims will be used to test this hypothesis: 1) Optimize and purify hybrids, 2) Using a panel of chemotherapies loaded into hybrids, evaluate the characteristics of the system, and 3) Determine the level of synergy between the formulations and radiation in the presence of cells with successful formulations being further tested in mice. The overall therapeutic implication is that the spatially and temporally specific delivery platform would allow for a synergistic therapy combining both radiation and chemotherapy to lower systemic toxicities and improve the efficacy and quality-of-life for patients.