Design and synthesis of multifunctional nanostructures for applications in medicine

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Our proposed research program is aimed at developing synthetic methodologies to well-defined nanostructures that work with the strategy, “seek a prevalent target to accumulate at the desired place, perform the task efficiently according to local needs, and disassemble”. Such smart nanomaterials are of crucial importance in a diverse range of areas, more specifically in nanomedicine. We focus on developing a unified chemical protocol that could be adapted to a variety of organic and inorganic structures. It facilitates a convergent approach to address complex biological problems by integrating understanding from imaging with delivery. Size and shape are two key parameters of importance in designing nanocarriers, and our research implements these in developing structure-property relationships. During the next five years, we shall design, synthesize, and carry out a detailed study of synthetically articulated functional structures. These will include a) macromolecules (branched, miktoarm polymers; hyperbranched, dendrimers; hybrids, telodendrimers); and b) gold nanoshell dimers. Nanostructures will be enabled with links that i) respond to and are cleaved by reactive oxygen species (thioketal); ii) generate terminal end groups that can be used to change morphology, when needed, through robust thiol-yne click chemistry at the site; and (iii) disassemble upon completion of their undertaking (ester hydrolysis). Stable nanocarriers carrying sufficient therapeutic payloads will target reactive oxygen species, a common marker at disease sites. The accumulating carriers will be empowered with the ability to further tailor their dimensions by generating inter-particle links in a biological medium. It will aid in their retention at the desired site, and limit non-specific distribution. Degradation and disassembly of nanoparticles after they have performed their intended task via acid/base hydrolysis, will assist in their removal. The gold nanoshell dimer based molecular imaging probe will provide high-resolution images for early detection, and determining the efficacy of nanoformulations in disease management. The integrated approach of the proposed research will generate fundamental knowledge that will expedite translation of functional nanostructures for biomedical applications, an area of great significance to Canada. It will create opportunities for the design of new advanced materials with consolidated functions. HQP with multidisciplinary skills will contribute to Canadian economy employed in diverse fields.