Atherosclerosis, inflammation of the arteries, is the underlying cause of most deadly cardiac events, such as strokes and heart attacks. Early and non-invasive diagnosis of atherosclerotic plaques will lead to better patient outcomes. To accurately detect plaques vulnerable to rupture, molecular imaging is required. Magnetic resonance imaging (MRI) provides the high spatial resolution and soft tissue contrast required to detect molecular markers on atherosclerotic plaques. Molecular MRI, however, requires high contrast agent accumulation due to its inherent low sensitivity. Nanoparticles are ideal platforms for cargo delivery, including contrast agents and therapeutics, because they can deliver large payloads to specific cells and tissues. We have turned toward the nanoparticles derived from plant viruses. Viral nanoparticles provide an excellent platform for cargo delivery because they are capable of chemical and genetic modification, easily attainable in various shapes and sizes, and designed by nature to deliver cargo to cells. Tobacco mosaic virus (TMV) presents a rod-shaped platform measuring 300 x 18 nm. TMV is capable of undergoing thermal transition to form spherical nanoparticles (SNPs), thus affording us the ability to test the structure-function relationship of targeting molecular markers under the unique physiological environment of atherosclerotic plaques. We have shown that covalent attachment of paramagnetic contrast agents, chelated Gd(DOTA), to TMV rods and spheres increases the ionic relaxivities of the agent. Mineralization of the Gd(DOTA)-modified TMV templates further increases the ionic relaxivity of Gd ions. In this presentation, we will discuss the engineering principles leading to TMV-based MRI contrast agents for detecting molecular markers on atherosclerotic plaques.

Optimizing tobacco mosaic virus rods and spheres for MRI detection of atherosclerotic plaques

248th National Meeting (2014)

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