Open AccessTargeting atherosclerosis by using modular, multifunctional micelles
Author(s) -
David G. Peters,
Mark Kastantin,
Venkata Ramana Kotamraju,
Priya Karmali,
Kunal V. Gujraty,
Matthew Tirrell,
Erkki Ruoslahti
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0903369106
Subject(s) - micelle , chemistry , in vivo , fluorophore , lysine , biophysics , pentapeptide repeat , biochemistry , fluorescence , amino acid , peptide , biology , physics , microbiology and biotechnology , quantum mechanics , aqueous solution
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.