期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 24, 页码 9815-9819出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0903369106
关键词
cysteine-arginine-glutamic acid-lysine-alanine; hirulog; plaque; imaging; nanoparicles
资金
- National Heart, Lung, and Blood Institute Program of Excellence in Nanotechnology [HL070818]
- National Center for Research Resources Shared Instrumentation [1S10RR017753]
- National Science Foundation Award [DMR05-20415]
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.
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