title: Active targeting of early and mid-stage atherosclerotic plaques using self-assembled peptide amphiphile micelles.
abstract: Inflammatory cell adhesion molecules expressed by endothelial cells on the luminal surface of atherosclerotic plaques, such as vascular cell adhesion molecule-1 (VCAM-1), provide a rational target for diagnostic and therapeutic delivery vehicles. Therefore, the potential of using spherical, self-assembled micelles synthesized from VCAM-1 targeted peptide amphiphile molecules was examined for the ability to specifically bind to both early and mid-stage atherosclerotic plaques. In vitro, cells incubated with VCAM-1 targeted and dye-labeled micelles show enhanced fluorescence signal as compared to cells incubated with a PEG micelle control. In vivo, VCAM-1 targeted and Cy7-labeled peptide amphiphile micelles were shown to specifically accumulate at atherosclerotic plaques in both early and mid-stage ApoE -/- mice through co-localization of Cy7 signal with anti-VCAM-1 antibody staining in fixed tissue. No specific accumulation was observed with a PEG micelle control. Histological analysis of excised tissue provided evidence for the in vivo biocompatibility of these micelle formulations as no tissue damage was observed. These results demonstrate that VCAM-1 targeted micelles have potential as a platform for targeted drug delivery to multiple stages of atherosclerotic plaque formation due to their established specificity and safety.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA; Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Mlinar
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Chung
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Wonder
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA. Electronic address: mtirrell@uchicago.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Tirrell
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008822:Mice, Transgenic; D008823:Micelles; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D058226:Plaque, Atherosclerotic / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D014018:Tissue Distribution / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D008823:Micelles; D010455:Peptides; D010714:Phosphatidylethanolamines; D013501:Surface-Active Agents; D019010:Vascular Cell Adhesion Molecule-1; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols
keywords: Atherosclerosis; Micelle; Peptide amphiphile; Self-assembly; VCAM-1