Aug 16, 2006
Nanoparticles could break up plaques in blood vessels
Researchers at Washington University School of Medicine, Philips Medical Systems, Bristol-Myers Squibb Medical Imaging and the University of Missouri Research Reactor, all in the US, have used nanoparticles to deliver a drug to artery-blocking plaques that can form in the bloodstream. The technique should enable the use of lower quantities of the plaque-busting drug fumagillin, which can have unpleasant side effects.
Atherosclerotic plaques form from a build up of cholesterol, inflammatory cells and fibrous tissue inside an artery. If the plaque breaks up, fragments of it may move round the body and block blood flow to the heart or brain, potentially causing a heart attack or stroke.
Fumagillin acts against plaques by restricting the growth of new blood vessels. Plaques develop their own blood supply in order to grow – they cause small blood vessels to generate within the artery wall and attach to the plaque. Many scientists believe that cutting off this blood supply could stabilize or reduce the plaques.
"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," said Patrick Winter of Washington University School of Medicine.
The team attached paramagnetic nanoparticles to the drug fumagillin, which has been shown to inhibit the growth of new blood vessels that feed atherosclerotic plaques. They also linked the nanoparticles to a component that attaches to cells found in the newly developing blood vessels. This caused the nanoparticles to concentrate at the desired site.
The particles were also visible by magnetic resonance imaging (MRI), potentially enabling doctors to check that the drug had reached the desired site and to measure how much had arrived, as well as to monitor treatment progress.
"Fumagillin can have neurocognitive side effects, causing injury to the brain at high doses," said Winter. "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 to be effective at a lower dose and clinically useful."
Although Winter and colleagues used a dose of fumagillin 50,000 times lower than employed in an earlier study, the treatment reduced the growth of new blood vessels in plaques by 60– 80%. The technique also seemed effective for early intervention.
"We wanted to go after the early stages of the disease when patients don't yet need immediate intervention to prevent serious cardiac problems," said Winter. "We think fumagillin nanoparticles potentially could be incorporated into a protocol that includes lipid-lowering statin drugs or dietary changes."
The researchers reported their work in Arteriosclerosis, Thrombosis, and Vascular Biology.
About the author
Liz Kalaugher is editor of nanotechweb.org.