Like mix-and-match facial features on a Mr. Potato Head, researchers at Washington University School of Medicine in St. Louis have developed a way to load microscopic particles, called nanoparticles, with a variety of useful things, including drugs. The technology may allow them to send imaging agents and medications directly to specific cells.
Washington University researchers at Barnes-Jewish Hospital recently received a three-year, $2.8 million contract from the National Cancer Institute to explore this technology, in collaboration with their industry partners, Kereos Inc., Royal Philips Electronics and the Dow Chemical Company. Gregory M. Lanza, M.D., Ph.D., assistant professor of medicine, is the principal investigator for the grant, which will fund research into this technology in conjunction with nuclear imaging techniques.
“You can load these nanoparticles with whatever you want, like a Mr. Potato Head,” says Samuel A. Wickline, M.D., professor of medicine and of biomedical engineering and one of the project’s principal investigators. “The technique soon may allow us to take non-invasive images of very early plaques in blood vessels, before they’re detectable by any other means. This same technology, we think, will allow us to detect very early cancers and other inflammatory events as well.”
Wickline and Lanza are co-founders of Kereos Inc., and are co-inventors of this nanoparticles technology.
Despite their remarkably small size of about 200 nanometers in length, nanoparticles can hold a surprisingly large number of other molecules.
For example, in research presented last year at the American Heart Association’s Scientific Sessions, the team discovered a way to take magnetic resonance images (MRI) that reveal the location of blood vessel plaques in rabbits, similar to atherosclerosis in humans.
To do that, they loaded a cluster of nanoparticles with about 80,000 atoms each of the element gadolinium, which shows up as a bright spot on an MRI. Other carriers for gadolinium hold only a few such atoms at a time, and therefore are not as bright on MRI scans.
In order for plaques to form, a crowd of smaller vessels, called capillaries, must develop around the diseased site. So Wickline and Lanza also packed each nanoparticle with molecules that specifically detect a protein called alphaVbeta3, which is abundant in rapidly growing capillaries. In doing so, the nanoparticles mainly latched onto cells that contain alphaVbeta3, and proceeded to label just those cells.
MRI scans taken of rabbits injected with these nanoparticles revealed clusters of miniscule, young blood vessels growing around plaques in the arteries.
“These preliminary results suggest that we can manipulate nanoparticles to image plaques as they are just beginning to form,” says Wickline. “Previous research of ours also suggests that this technique can distinguish between patients with stable plaques and those whose plaques are about to rupture and thereby cause a heart attack or stroke.”
Because tumors also require new populations of capillaries, the team believes this technique will enable them to detect early cancers at the very beginning stages of tumor development. It also may allow them to deliver cancer drugs directly to tumor cells, thereby minimizing the damaging effects of these drugs on healthy cells in the rest of the body. Their contract from the National Cancer Institute will fund further exploration into this potential cancer application.
“If we are successful,” says Lanza, “this technique will provide the next ‘state of the art’ in cancer detection, diagnosis and care.”
The technology used in these studies has been licensed to KEREOS Inc., which is devoted to molecular imaging and targeted therapeutics. Gregory M. Lanza, M.D., Ph.D., and Samuel A. Wickline, M.D., are co-founders of KEREOS and both are board members and equity holders.
Kereos is developing targeted therapeutics and imaging agents that seek out molecular markers highly specific for various diseases, based upon nanoparticle technology developed by Drs. Wickline and Lanza and licensed from Barnes-Jewish Hospital. Utilizing this proprietary platform, these products should permit more effective diagnosis and targeted treatment of a broad range of human disorders. The company’s initial clinical focus is on cancer and cardiovascular disease.
About Royal Philips Electronics:
Royal Philips Electronics of the Netherlands is one of the world’s biggest electronics companies and Europe’s largest, with sales of $30.1 billion (EUR 31.8 billion) in 2002. It is a global leader in color television sets, lighting, electric shavers, medical diagnostic imaging and patient monitoring, and one-chip TV products. Its 170,000 employees in more than 60 countries are active in the areas of lighting, consumer electronics, domestic appliances, components, semiconductors, and medical systems. Philips is quoted on the NYSE (symbol: PHG), London, Frankfurt, Amsterdam and other stock exchanges.
Dow is a leading science and technology company that provides innovative chemical, plastic and agricultural products and services to many essential consumer markets. With annual sales of $27 billion Dow serves customers in more than 170 countries and a wide range of markets that are vital to human progress, including food, transportation, health and medicine, personal and home care, and building and construction, among others. Committed to the principles of Sustainable Development, Dow and its approximately 50,000 employees seek to balance economic, environmental and social responsibilities.