March 6, 2006
Dog Virus Nanoparticles Adapted for Tumor Targeting
Empty virus particles have shown promise as potential nanoscale drug carriers that can be modified chemically to display tumor-targeting molecules. Now, investigators at The Scripps Research Institute have shown that canine parvovirus nanoparticles, which bind to a receptor that is overproduced by some types of malignant cells, will naturally target tumors.
Writing in the Journal of Nanobiotechnology, a team led by Marianne Manchester, Ph.D., describes its studies aimed at determining whether mass-produced, non-infectious canine parvovirus nanoparticles might be suitable as a tumor-targeting drug delivery vehicle through the particles’ natural interaction with transferrin, a receptor that carries iron into cells. The reproducible size and chemical makeup of virus-based nanoparticles, combined with the relative ease of manufacturing them in large quantities, make them possible winners in the drive to develop nanoparticulate drug carriers for cancer therapy. Such laudable properties are only of use, however, if these protein nanoparticles can be modified to carry small molecules into tumor cells.
The investigators began by analyzing the structure of protein that assembles into viral nanoparticles. This evaluation showed that there should be at least two, and perhaps as many as six, amino acids on the surface of this protein that should be available to react chemically with small drug molecules or imaging agents. Since 60 copies of this protein come together to form the final virus nanoparticle, the investigators reasoned that it should be relatively straightforward to attach clinically useful molecules to the virus nanoparticles.
Indeed, using a green fluorescent dye as a model for a drug molecule, the investigators were able to develop chemical methods to attach between 45 and 100 dye molecules to the surface of each nanoparticle. Equally as important, the research team designed a mild purification procedure that left the resulting labeled nanoparticles intact.
Next, Manchester and her colleagues studied how efficient the nanoparticles were at ferrying the attached dye molecule into various tumor cells. These experiments, using three different types of cultured cancer cells, showed that the nanoparticles were capable of binding to the transferrin receptor on tumor cells, and that this resulted in the rapid uptake of the nanoparticles. Canine parvovirus nanoparticles were not taken up by tumor cells that do not express the transferrin receptor.
This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Canine parvovirus-like particles, a novel nanomaterial for tumor targeting.” This paper is available free of charge through the journal’s website.