Imagine a human-made sphere so small that you could wrap dozens of them around a red blood cell. Picture particles so tiny they could slip through pores in blood vessels and lodge themselves into a tumor. Researchers at Ohio State University are studying such nanospheres for their ability to enhance ultrasound images and possibly aid in the clinical diagnosis of cancer.
Thomas Rosol and Jun Liu examined the imaging proper ties of spheres about 100 nanometers in diameter after inject ing them into the tail veins of mice. The nanospheres, delivered in a watery suspension, traveled throughout the circulatory system and accumulated in the liver, where they were collected by bacteria-destroying cells. Once in the liver, the nanospheres enhanced tissue reflectivity when examined through ultrasound. Changes in liver reflectivity could be seen 15 minutes after injection and lasted for up to 1.5 hours.
Rosol and Liu found that brightness of the liver tissue was directly correlated to the concentration of nanospheres delivered. Their data suggest that nanospheres can indeed be used as tiny imaging agents.
Nanospheres are ideally sized for clinical use because bigger particles, those larger than a micron, are quickly recognized and cleared by the body. Nanospheres not only temporarily evade recognition-thus providing extended time for imaging-but also are small enough to fit through the pores of a tumor's leaky blood vessels and reach its cells.
In future studies, Rosol and Liu plan to attach the nanospheres to antibodies that bind to tumor cells. A large concentration of these nanosphere-labeled antibodies, lodged in a small tumor lesion, could then be detected via ultrasound. "Traditionally, ultrasound cannot see very small lesions. So the goal is to use the nanospheres to detect these lesions before the tumor starts to get too big," says Rosol.
Rosol and Liu noted no adverse effects of the nanospheres up to two weeks post-injection. "These particles are so small that they are taken up by the macrophages and can be eliminated through the lungs or the gastrointestinal system. Nonetheless, we eventually want to use biodegradable nanoparticles," says Rosol.
Rosol's research was supported through NCRR's Mid career Investigator Award (K26) in Mouse Pathobiology Research, which he has leveraged to obtain additional fund ing. "By using preliminary data from the grant, we were successful in obtaining a Shared Instrumentation Grant from NCRR to purchase a Micro CT scanner," he says. The K26 award allows established pathobiologists, like Rosol, to spend up to 50 percent of their time performing research and mentoring the next generation of mouse pathobiologists. (Phys. Med. Biol. 51:2179-2189, 2006)
—Al Staropoli