Targeting atherosclerosis by using modular, multifunctional micelles.
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.
Peters
David
D
Vascular Mapping Center, Burnham Institute for Medical Research, University of California, Santa Barbara, 3119 Biology II Building, CA 93106-9610, USA.
Kastantin
Mark
M
Kotamraju
Venkata Ramana
VR
Karmali
Priya P
PP
Gujraty
Kunal
K
Tirrell
Matthew
M
Ruoslahti
Erkki
E
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
D001057:Apolipoproteins E; D008823:Micelles