June 26, 2006
Coated Virus Nanoparticles Boost MRI Signals
Virus particles, with their well-characterized nanoscale structures and ease of large-scale production, have become a popular tool for cancer nanotechnology researchers (click here for earlier stories) aiming to develop targeted antitumor therapies. A new study, published in the journal Nano Letters, adds to this growing toolbox with the demonstration that a bacterial virus, known as a bacteriophage, can be turned into a powerful magnetic resonance imaging (MRI) agent.
Kent Kirshenbaum, Ph.D., and colleagues at New York University School of Medicine, used the outer coat of the bacteriophage virus, known as MS2, as their base nanoparticle. This protein shell, which the investigators mass-produced in a genetically engineered strain of E. coli, contains 180 identical proteins that self-assemble into a 27.4-nanometer-diameter particle. Using a fluorescent dye as a marker, the investigators then determined that there are 1,080 identical chemically reactive sites on the surface of the assembled nanoparticle. They used these sites as attachment points for adding a gadolinium-chelating agent. A chelating agent is a molecule that tightly binds to one or more metal ions, in this case the MR imaging agent gadolinium. After adding the gadolinium-chelating agent, each nanoparticle contained an average of 514 gadolinium ions on its surface.
The researchers also prepared a multifunctional imaging agent by first attaching approximately 50 fluorescent dye molecules to the nanoparticle surface using mild chemical conditions. They then used the remaining attachment sites to add 360 gadolinium ions. Both the gadolinium-coated nanoparticles and the dual-function nanoparticles were stable for over a month. The researchers noted that other types of chemical reactions could be used to attach drug and tumor-targeting molecules to the viral coat as well.
Measurements using magnetic field strengths typical of standard clinical MR imaging devices showed that MR signal enhancement was up to 1,000 times stronger than that produced by any currently used MR contrast agent. The investigators characterized the fluorescent signal they obtained using the dual-function nanoparticle as “highly intense.”
This work is detailed in a paper titled, “Viral nanoparticles donning a paramagnetic coat: conjugation of MRI contrast agents to the MS2 capsid.” Investigators from the University of New Mexico also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s website.