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Targeting atherosclerosis by using modular, multifunctional micelles.

ABSTRACT: Subtle clotting that occurs on the luminal surface of atherosclerotic plaques presents a novel target for nanoparticle-based diagnostics and therapeutics. We have developed modular multifunctional micelles that contain a targeting element, a fluorophore, and, when desired, a drug component in the same particle. Targeting atherosclerotic plaques in ApoE-null mice fed a high-fat diet was accomplished with the pentapeptide cysteine-arginine-glutamic acid-lysine-alanine, which binds to clotted plasma proteins. The fluorescent micelles bind to the entire surface of the plaque, and notably, concentrate at the shoulders of the plaque, a location that is prone to rupture. We also show that the targeted micelles deliver an increased concentration of the anticoagulant drug hirulog to the plaque compared with untargeted micelles.

SUBMITTER: Peters D

PROVIDER: S-EPMC2689312 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Targeting atherosclerosis by using modular, multifunctional micelles.

Peters David D Kastantin Mark M Kotamraju Venkata Ramana VR Karmali Priya P PP Gujraty Kunal K Tirrell Matthew M Ruoslahti Erkki E

Proceedings of the National Academy of Sciences of the United States of America 20090601 24

Subtle clotting that occurs on the luminal surface of atherosclerotic plaques presents a novel target for nanoparticle-based diagnostics and therapeutics. We have developed modular multifunctional micelles that contain a targeting element, a fluorophore, and, when desired, a drug component in the same particle. Targeting atherosclerotic plaques in ApoE-null mice fed a high-fat diet was accomplished with the pentapeptide cysteine-arginine-glutamic acid-lysine-alanine, which binds to clotted plasm ...[more]

PMID: 19487682

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