Grant: Banting Postdoctoral Fellowship Program

A perennial challenge in cancer therapy is the delivery of a drug to a tumour while sparing its effects on normal tissue. Among the many approaches are those that exploit the way in which new blood vessels develop in solid tumours to become disorganized, immature and 'leaky' to particles below a particular size, which allows drugs encapsulated in very small carriers (or liposomes) to accumulate selectively. This strategy faces a number of obstacles which this project aims to overcome with novel acoustical techniques. First among these is the effect of the heterogeneity of the blood supply and the tendency of solid tumours to push fluid away from them, thus making it hard to distribute a drug uniformly. Medical ultrasound offers a unique solution to these issues. When combined with microscopic bubbles, ultrasound can interact mechanically with the vessel walls and the tumour tissue in a way that we hypothesize can distribute drugs throughout the mass. We propose to develop a new ultrasound-based platform for drug delivery which centers on precise design of particles that circulate in the bloodstream and are activated by ultrasound only at the cancer site. These nanoparticles then convert to microbubbles that modify the local tissue properties and increase the efficacy of drug delivery. We will tailor the particles to have desired circulatory properties and acoustic activation thresholds, giving high control over when and where drugs are deposited. While we will focus on liposomal drug delivery to solid tumours, the techniques will be generally applicable to a wide range of tumour types and therapeutic agents. Successful completion of this project will provide a novel drug delivery platform ready for clinical translation which should advance the field of ultrasound-mediated therapy significantly. Strategies for clinical implementation of these concepts will be investigated in collaboration with researchers at Canada's largest comprehensive cancer centre in Toronto.