June 12, 2006
Targeted Nanoparticle Enhances MRI Detection of Cancer Cells
Using a novel polymer to coat paramagnetic iron oxide particles, a research team at the University of Washington in Seattle has created a nanoparticulate magnetic resonance (MR) imaging agent that targets certain tumor cells. The polymer coating, a derivative of the biocompatible polymer poly(ethylene glycol), or PEG, self-assembles on the surface of the iron oxide nanoparticles and provides a stable attachment site for targeting molecules.
Writing in the Journal of Biomedical Materials Research Part A, a group led by Miqin Zhang, Ph.D., principal investigator of one of the National Cancer Institute’s Cancer Nanotechnology Platform Partnerships, describes its use of a custom-made low-molecular-weight version of PEG that contains two different reactive groups, one of which reacts with the surface of the iron oxide nanoparticle, while the other remains free as an attachment point for targeting molecules. The use of a low-molecular-weight version of PEG maximizes the density of the resulting surface coating while leading to a smaller final size for the coated nanoparticle. Smaller nanoparticles may be taken up more efficiently by cells than larger nanoparticles while better evading elimination by the immune system.
Once the investigators prepared the coated nanoparticles, they attached folic acid to act as a cancer cell targeting agent. Experimental results showed that tumor cells that overexpress the folic acid receptor took up 12 times more of the targeted nanoparticles than they did other nanoparticles coated with either unmodified PEG or with the polymer dextran.
In addition, the folic-acid-expressing tumor cells were up to 10 times more efficient at taking in the targeted nanoparticles than were tumor cells deficient in folic acid receptors. Adding free folic acid to the incubation medium competed with the targeted nanoparticles for access to the folic acid receptor, blocking the uptake of the nanoparticles. Nanoparticles inside the tumor cells were readily visible in MRI scans.
This work, which was funded in part by the National Cancer Institute, is detailed in a paper titled, “Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI.” This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.