Development of stabilized environmentally sensitive polymeric nanoparticles

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Research Problem: Nanoparticles have been extensively explored as carriers to deliver hydrophobic molecules to targeted locations. Hydrophobic molecules do not disperse easily in water and can aggregate, thereby compromising their efficacy. Nanoparticles overcome this challenge by offering a hydrophobic core for hydrophobic payloads, while providing a hydrophilic shell that promotes free dispersion in aqueous solution. Nanoparticles offer the additional benefit to improve payload stability by encapsulating cargos to avoid adverse contact with destabilizing agents before their destination. Recently, progress has been made in developing environmentally sensitive nanoparticles that release their payloads in response to environmental stimuli, which can be either chemical (pH, redox) or physical (temperature, light). Improving the stability and loading efficiency of nanoparticles is a key consideration for a variety of applications. Proposed Research: My work is aimed at developing synthetic polymeric nanoparticles that are environmentally sensitive. They remain stable until they are exposed to an environment characterized by low pH, a high reducing potential or a temperature change. These nanoparticles will have potential applications as carriers of bioactive agents to treat diseases or to monitor biological processes as a biosensor. The goal of the proposed program is to design biopolymers for stabilized nanoparticles with environmental sensitivities. Polymeric nanoparticles will be synthesized with a hydrophobic core and a hydrophilic shell. Redox, pH, and temperature sensitivities will be introduced into the polymers. The rationale is that the nanoparticles can be designed to efficiently release their cargos upon exposure to one or several of these stimuli in a pre-programmed manner. For example, pH and redox sensitivities can facilitate intracellular delivery of cargos due to the low pH value and high level of reducing agents in the intracellular environment. In addition, temperature change can lead to a morphology change of nanoparticles that can promote cargo release. The proposed research will also improve the stability of nanoparticles by studying different crosslinking methods and comparing their effects on stability and payload release. In order to study the effects of hydrophobicity on encapsulation, we will study different hydrophobic molecular chains and assess the resulting loading efficiency. Expected Outcome: The research program will optimize the structure and performance of polymeric nanoparticles as carriers of chemical agents, and will also advance our knowledge of functional polymers with environmental sensitivities. This research has the potential to promote the growth of the Canadian Nanomaterials Industry by developing a wealth of new materials. The proposed program will provide cutting edge training for HQP at different levels.