Development and Application of a Rod and Sphere-Shaped Viral Nanoparticle MRI Contrast Agent for Atherosclerosis Diagnosis

M.A. Bruckman, N.F. Steinmetz
Case Western Reserve University, US

Keywords: viral nanoparticle, MRI, atherosclerosis


The use of nanoparticles to deliver magnetic resonance (MR) contrast agents to enhance MR sensitivity has shown great potential in identifying and diagnosing diseases such as cancer and cardiovascular disease. A common challenge is the fabrication of nanoparticles with well-defined properties, such as morphology, size, charge, and surface functionalities. Tobacco mosaic virus (TMV) presents a hollow rod-shaped platform measuring 300 by 18 nm, capable of undergoing chemical conjugation to its interior and exterior surfaces. Recently, it was found that TMV undergoes thermal transition to form RNA-free spherical nanoparticles (SNPs) upon heating for a short time period. Here, we show that TMV can be loaded with thousands of paramagnetic gadolinium (Gd) ions to enhance MR sensitivity. Upon conjugation of chelated Gd compounds, the ionic relaxivity is significantly enhanced. Finally, atherosclerotic plaques in a mouse model were imaged with MRI using a targeted formulation of Gd loaded TMV. These results represent the most sensitive and the first rod-shaped viral nanoparticle MRI contrast agent to date. Aside from using carbon nanotubes, TMV based MRI contrast agents have the highest aspect ratio for rod-shaped nanoparticles, of which there are very few options.