December 11, 2006
Combination Nanoparticle Provides Imaging and Treatment Capabilities
Alloys of iron and cobalt generate powerful magnetic signals that could be useful in nanoparticles designed to detect tumors using magnetic resonance imaging (MRI). However, naked iron-cobalt nanoparticles turn out to be chemically active materials, making them unsuitable for use in the body, and efforts to add any number of protective coatings have failed to produce biocompatible nanoparticles.
To solve this problem, researchers at the Center for Cancer Nanotechnology Excellence Focused on Therapy Response, based at Stanford University, used a high-temperature vapor deposition process to construct a carbon-coated iron/cobalt nanoparticle that can safely image tumors in living animals. Moreover, these nanoparticles can absorb near-infrared light and generate heat, raising the possibility that they could not only image tumors, but kill them by cooking them to death. The results of this effort appear in the journal Nature Materials.
Hongjie Dai, Ph.D., and his colleagues created their carbon-coated nanoparticle by first loading iron- and cobalt-containing molecules onto silica powders. They then took this material, heated it to 800° C, and added methane gas into the reaction chamber. After cooling the reaction mixture, the researchers added a polymer coating that rendered the nanoparticles soluble in water. These nanoparticles were stable in water for more than six months.
Using electron microscopy, the researchers were able to characterize the resulting particles as having a core-shell structure whose final diameter depended on the amount of metal loaded initially onto the silica particles. Based on characterization data, the investigators believe that upon heating, the iron and cobalt molecules undergo a chemical reaction that generates a stable iron-cobalt alloy on nanoscale silica particles. Methane molecules then react with this alloy, forming a thin shell of graphite around the metal-coated silica particles.
After demonstrating that these nanoparticles had suitable magnetic and optical properties, the investigators showed that cultured cells spontaneously took in the nanoparticles, an event that was seen easily using MRI. Preliminary toxicology studies revealed no obvious problems associated with repeated injections over a period of six months.
Based on these experiments, the Stanford team then injected the nanoparticles into rabbits and showed that they could image the animals’ blood system over a period of 20 minutes. In comparison, conventional MRI imaging agents containing gadolinium remain in circulation for less than one minute. In addition, the researchers were able to obtain useful images using only 10 percent of the metal dose typically used with gadolinium-based contrast agents. The researchers predict that they will be able to target these nanoparticles to tumors, providing the ability to image cancer using MRI and treat cancer using near-infrared light-activated thermal therapy. Near-infrared light can travel several centimeters through biological tissue.
This work, which was supported by the NCI’s Alliance for Nanotechnology in Cancer, is detailed in a paper titled, “FeCo/graphitic-shell nanocrystals as advanced magnetic-resonance-imaging and near-infrared agents.” An abstract of this paper is available through PubMed.