Graduate Research - Targeted Imaging

Cardiovascular diseases present a serious threat to human health, with nearly one in three deaths in the United States attributable to these afflictions. The development of atherosclerosis targeted imaging agents has the capability to provide molecular information about pathological clots, potentially improving detection, risk stratification, and therapy of cardiovascular diseases. Nanocarriers are a promising platform for the development of molecular imaging agents as they can be modified to have external targeting ligands and internal functional cargo. I synthesized chemically functionalized bacteriophase MS2 capsids as protein-based nanoparticles for fibrin and vascular cellular adhesion molecule 1 (VCAM1) imaging. The capsids were modified using an oxidative coupling reaction, conjugating ~90 copies of targeting peptides to the exterior of each protein shell. The ability of the multivalent, targeted capsids to bind fibrin was first demonstrated by determining the impact on thrombin-mediated clot formation. The modified capsids out-performed the free peptides and were shown to inhibit clot formation at effective concentrations over ten-fold lower than the monomeric peptide alone. The installation of near-infrared fluorophores on the interior surface of the capsids enabled optical detection of binding to fibrin clots. The targeted capsids bound to fibrin, exhibiting higher signal-to-background than control, non-targeted MS2-based nanoagents.