Nanotech News
October 10, 2005
Virus Nanoparticles Provide Convenient Oral Drug Delivery Vehicle
Viruses by their very nature are well-defined nanoparticles, and several teams of investigators are taking a cue from nature and developing non-infectious, engineered viral nanoparticles for use as multifunctional nanoscale devices. The plant virus known as cowpea mosaic virus (CPMV) has become a researcher favorite, in large part because it is relatively easy to produce in large amounts, and the virus is benign to humans and other animals. In addition, researchers have developed methods of altering the virus’s coat protein to give it chemical functionality that might be useful for adding targeting and drug delivery capabilities to these nanoparticles.
Now, there’s another reason to study CPMV particles as potential biomedical nanodevices. Marianne Manchester, Ph.D. and M.G. Finn, and their colleagues at the Scripps Research Institute have shown that CPMV nanoparticles can pass intact through the stomach’s hostile environment and be taken into the bloodstream through the intestines. As a result, CMPV nanoparticles could provide a means of administering anticancer drugs and tumor imaging agents by mouth, rather than by injection. This work appeared in the journal Virology.
In most studies, researchers produce CPMV nanoparticles using a system that makes just the proteins that the virus uses to make its outer shell – these proteins self-assemble to make the virus’s shell. But to learn what would happen to CPMV particles as they pass through the digestive system, the researchers used the fully formed virus, complete with its RNA genetic material. Having the RNA present allowed the investigators to use PCR-based technology to detect very small number of particles no matter what part of the body they reached. Indeed, after feeding mice cowpea leaves infected with the virus, the investigators found virus particles distributed widely throughout the animals’ bodies.
Subsequent studies using analytical techniques to detect the virus coat proteins confirmed that the virus particle, and not just its genetic material, had passed through the stomach, been absorbed through the intestines, and distributed itself throughout the animal. Nearly identical results were obtained when the virus was injected directly into the bloodstream of the test animals, supporting the idea that virus particles were able to pass through the intestines unaltered. In vitro experiments also showed that engineered CPMV particles are stable in conditions that mimic the acidic conditions of the stomach.
Taken together, these data support the notion that engineered, synthetic plant virus particles could prove useful in delivering drugs and imaging contrast agents to tumors. Previous work by the Manchester and Finn groups have already shown that it is possible to attach tumor-targeting molecules to the surface of engineered viral nanoparticles and to load various drug-type molecules into the interior of the virus particles.
This work, which was supported by the National Cancer Institute, was detailed in a paper titled, “Systemic trafficking of plant virus nanoparticles in mice via the oral route.” An investigator from the University of Germaneto, in Catanzaro, Italy, also participated in this study. An abstract is available through PubMed. |
