A scientist in Missouri has developed a novel use for nanoparticles: diagnosing atherosclerosis.
Atherosclerosis is the narrowing of the arteries caused by fatty plaque buildup, which can eventually break off and cause blood clots in the heart or brain, leading to heart attack or stroke.
Biomedical engineer Shelton Caruthers and his team at Washington University in St. Louis are short-circuiting this deadly progression using nanoparticles to detect arterial obstructions before they can cause serious damage. Caruthers presented the group's findings recently at the International Congress of Nanotechnology in San Francisco.
Magnetic-resonance imaging can reveal atherosclerosis, but the condition often is found only after the patient has suffered a heart attack or stroke. Caruthers' early-detection solution is to inject patients with 200-nanometer-long particles whose surfaces are modified to bind to avb3, a proteinlike compound the body uses to form new blood vessels.
Because arterial plaques spawn networks of capillaries that supply them with the oxygen and nutrients they need to grow, the avb3-binding nanoparticles cluster in areas where plaques are beginning to form.
"We can put different things on the surfaces of these particles, just like on a Mr. Potato Head," Caruthers said. "As the particles pass by the vessels, they stick and hold, because there's a molecular arm that grabs onto the avb3."
Each injected nanoparticle is loaded with about 80,000 atoms of gadolinium, a chemical that emits a distinctive whitish glow on a magnetic-resonance scan. "You can't see it right away, but as the particles circulate, they start to accumulate," Caruthers said. After about two to four hours, enough of the glowing particles have amassed to enable a doctor to easily pinpoint the locations of new plaque deposits.
To test the effectiveness of the targeted particles, the team put white rabbits on a high-cholesterol diet for 80 days, then injected them with avb3-targeting nanoparticles. When the researchers took MRI images of the animals' abdominal aortas -- one of the largest arteries in the body -- they could clearly see clumps of nanoparticles surrounding diseased areas of the vessels. A control group of rabbits that had been fed a normal diet during the treatment period showed no such accumulations.
Caruthers and his colleagues, including project leaders Patrick Winter and Samuel Wickline, think their technique will eventually be used to screen patients suspected to be in the initial phases of cardiovascular disease.
"The hope is to detect disease earlier, which should lead to more effective treatment," Caruthers said.
Kereos, a molecular-imaging company based in St. Louis, has plans to bring the particles to market eventually. Al Beardsley, the company's CEO, is discussing Caruthers' findings with some pharmaceutical companies. He estimates human clinical trials could begin in the next few years.
What's still unclear at this point, Beardsley believes, is how early detection of cardiovascular disease will affect treatment strategies. Currently, many doctors recommend an invasive surgery known as an endarterectomy to get rid of arterial plaque deposits.
Caruthers is working on figuring out the answer to that question. He's recently been conducting experiments that involve loading nanoparticles with paclitaxel, a chemical that kills newly forming vascular muscle cells. When they enter the bloodstream, he said, these particles "reduce new blood vessel formation, which also reduces the amount of plaque growth that can take place."
