Nanotech News

October 3, 2005

MRI Contrast Agents from Viral Nanoparticles

By stuffing a harmless virus particle with dozens of slightly magnetic metal ions, a multi-institutional research team has developed a powerful tool that may be capable of detecting microscopic tumors at their most treatable stage. This work, which has been published in the journal Magnetic Resonance in Medicine, takes advantage of the fact that the proteins that make up the outer shell of virus particles have a strong affinity for binding to metal ions.

Magnetic resonance imaging (MRI) has already proven itself a useful tool for detecting tumors, but its ability to detect the smallest tumors is hampered by a lack of sensitivity that is inherent in the way that the MRI process detects the difference between malignant and normal tissue. One solution to the sensitivity problem is to use nanoparticles that are targeted to tumors and loaded with magnetic metal ions such as gadolinium. The metal ions act as signal enhancers, also known as contrast agents, that greatly boost the MRI signal.

While other groups have used dendrimers, polymer nanoparticles, and carbon nanotubes as vehicles for gadolinium ions or iron oxide nanocrystals, a group headed by Trevor Douglas, Ph.D., and Mark Young, Ph.D., both at Montana State University, used the cowpea chlorotic mottle virus (CCMV), which infects only plants and which can be produced easily in large quantities, and the metal ion carrier. The proteins on the CCMV shell, or coat, are capable of binding as many as 180 metal atoms. In addition, other segments of these coat proteins can be used to attach molecules that could target the metal-loaded virus particles to tumors, while the empty interior of the virus particle can be used to ferry drug molecules to tumors.

Coating the viral particles, which lack any viral DNA, with gadolinium was accomplished simply by adding viral particles to a solution of gadolinium in water. An analysis of the resulting formulation showed that the gadolinium ions were bound to the viral particle with sufficient strength that gadolinium would be expected to remain attached to the particle under physiological conditions. This is important because free gadolinium ions can be toxic to cells. Planned in vivo experiments aim to confirm this prediction.

MRI measurements on the gadolinium-CCMV complex demonstrated that it had superior properties as a contrast agent. Compared to other gadolinium-loaded nanomaterials, the CCMV formulation produced between 5- and 10-fold higher signal enhancement.

This work is detailed in a paper titled, "Paramagnetic viral nanoparticles as potential high-relaxivity magnetic resonance contrast agents." Investigators from the Johns Hopkins University School of Medicine, the National Institutes of Health Clinical Center, and the Bose Institute in Calcutta, India, also participated in this study. This paper was published online in advance of print publication. An abstract is available through the journal's website.
View abstract.