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Targeted Micelles Home in on Atherosclerotic Plaques

By LabMedica International staff writers
Posted on 15 Jun 2009
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Image: Colored scanning electron micrograph (SEM) of a section through a human coronary artery showing atherosclerotic plaque (Photo courtesy of Prof. P.M. Motta, G. Macchiarelli, S.A. Nottola / SPL).
Image: Colored scanning electron micrograph (SEM) of a section through a human coronary artery showing atherosclerotic plaque (Photo courtesy of Prof. P.M. Motta, G. Macchiarelli, S.A. Nottola / SPL).
Cardiovascular disease researchers used targeted micelles to deliver anticoagulant drugs directly to atherosclerotic plaques that developed in the arteries of mice fed on a high-fat diet.

Investigators from the University of California, Santa Barbara (USA) worked with ApoE-null mice fed a high-fat diet. They treated these animals with nanoparticle micelles that comprised a targeting element, a fluorophore, and a drug component. The targeting element was the pentapeptide cysteine-arginine-glutamic acid-lysine-alanine, which binds to coagulated plasma proteins.

Results published in the June 1, 2009, online issue of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS) revealed that while the fluorescent-labeled micelles bound to the entire surface of the plaques, they concentrated at the shoulders of the plaques, the area most prone to rupture. In addition, the targeted micelles delivered an increased concentration of the anticoagulant drug hirulog to the plaques compared with untargeted micelles.

"One important element in what we did was to see if we could target not just plaques, but the plaques that are most vulnerable to rupture,” said senior author Dr. Erkki Ruoslahti, professor of biological sciences at the University of California, Santa Barbara. "It did seem that we were indeed preferentially targeting those places in the plaques that are prone to rupture. The plaques tend to rupture at the "shoulder,” where the plaque tissue meets the normal tissue. That is also a place where the capsule on the plaque is the thinnest, so by those criteria, we seem to be targeting the right places. The purpose of our grant is to develop targeted nanoparticles that specifically detect atherosclerotic plaques. We now have at least one peptide, described in the paper, which is capable of directing nanoparticles to the plaques.”

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