title: 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.
authors.affiliation: Vascular Mapping Center, Burnham Institute for Medical Research, University of California, Santa Barbara, 3119 Biology II Building, CA 93106-9610, USA.
authors.forename: David
authors.initials: D
authors.lastname: Peters
authors.forename: Mark
authors.initials: M
authors.lastname: Kastantin
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Kotamraju
authors.forename: Priya P
authors.initials: PP
authors.lastname: Karmali
authors.forename: Kunal
authors.initials: K
authors.lastname: Gujraty
authors.forename: Matthew
authors.initials: M
authors.lastname: Tirrell
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D050197:Atherosclerosis / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D051379:Mice; D018345:Mice, Knockout; D008823:Micelles
chemical_list: D001057:Apolipoproteins E; D008823:Micelles