Targeting atherosclerosis by using modular, multifunctional micelles.
- Authors
- Type
- Published Article
- Journal
- Proceedings of the National Academy of Sciences
- Publisher
- Proceedings of the National Academy of Sciences
- Volume
- 106
- Issue
- 24
- Pages
- 9815–9819
- Identifiers
- DOI: 10.1073/pnas.0903369106
- Source
- Ruoslahti Lab
- License
- Unknown
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.