The long-term goal of the proposed research is to enable magnetic resonance imaging (MRI) of protease-associated human diseases, particularly carcinogenesis. New activatable MRI agents will be designed that will allow physicians to detect and treat cancer earlier. Specifically, iron oxide nanoparticles will be functionalized with surface modifications that can be used to induce MR signal contrast via aggregation of these superparamagnetic nanoparticles. Two biomimetic molecular binding partners will be investigated in an effort to uncover a mechanism by which to trigger nanoparticle aggregation upon the activity of physiologically important and disease-associated proteases. Protease-sensitive peptide sequences will be rationally engineered into the orthogonal molecules in order to mask nanoparticle aggregation until proteolytic cleavage. The availability of protease-induced aggregating nanoparticles will provide new tools to monitor the development and progression of protease-associated diseases in vivo.

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