Nanotargeting Atherosclerotic Plaques

Here is another example of the future possibilities of nanotechnology. Investigators from the Washington University School of Medicine embedded the drug fumagillin into nanoparticles and targeted the growth of new blood vessels (angiogenesis) in atherosclerotic plaques. Fumagillin is an antiangiogenesis drug.

“Previously we reported that we can visualize plaques using our nanoparticle technology, but this is the first time we’ve demonstrated that the nanoparticles can also deliver a drug to a disease site in a living organism,” says Patrick Winter, Ph.D., research assistant professor of medicine. “After a single dose in laboratory rabbits, fumagillin nanoparticles markedly reduced the growth of new blood vessels that feed plaques.”
The researchers report their findings in the September issue of the journal Arteriosclerosis, Thrombosis, and Vascular Biology, and the article is now available on line.
An atherosclerosis plaque results when a buildup of cholesterol, inflammatory cells and fibrous tissue forms inside an artery. If a plaque ruptures, it can block blood flow to the heart or brain, causing heart attack or stroke.
While growing, plaques require an influx of nutrients, fats and cells, so they develop their own blood supply — minute blood vessels that grow within the wall of arteries and penetrate the plaque. Many believe that cutting off this blood supply could stabilize or reduce plaques. In previous studies, fumagillin has been shown to be an effective agent for stopping the process that creates new blood vessels.
Riding on the nanoparticles, fumagillin is carried to the site of new blood vessel formation and stays there thanks to a fellow nanoparticle passenger — a component that fastens the nanoparticles to cells found in newly developing blood vessels. Stuck in this position, the nanoparticle drops its load of fumagillin, concentrating it at the site of the atherosclerotic plaque.
In this study, the single dosage of fumagillin each rabbit received was 50,000 times lower than the total fumagillin dose used in an earlier experiment by another research group and yet reduced the growth of new blood vessels in plaques by 60 to 80 percent.
“Fumagillin can have neurocognitive side effects, causing injury to the brain at high doses,” Winter says. “The ability of the nanoparticles to concentrate the drug at the disease site allows the dose to be lowered. This could open the door for a lot of drugs that have failed to be approved because they caused too many side effects at a higher dose. It might pay to look at these drugs again and ask if placing them on these nanoparticles can help them be effective at a lower dose and clinically useful.”
In the current study, the researchers fed rabbits a high-cholesterol diet for 80 days before treatment with fumagillin nanoparticles. The diet caused numerous small plaques in the rabbits’ aortas, but the plaques were considered to be at an early stage of growth. By demonstrating the utility of the nanoparticles for early intervention of atherosclerosis, the research group hopes that they can help alleviate the need for more invasive treatment of later-stage atherosclerosis.

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