Abstract 001: The Investigation of Peptide Amphiphile Micelles for Detection of Vulnerable Atherosclerotic Plaques
Atherosclerosis is an inflammatory disease that is complicated by progressively unstable plaques which are characterized by specific molecular events. While current diagnostic imaging technology aim to determine the stability of plaques by assessing their physical attributes, molecular imaging tools aim to assess the true nature of the plaque through targeting of molecular markers. Furthermore, these existing technologies can hardly meet the sensitivity and accuracy standards that are required for any clinical application for preventive measures.
In order to preventatively intervene during the early pathology of plaque vulnerability, we are engineering monocyte-targeting, fluorescently-labeled peptide micelles (MFPMs) through the incorporation of the chemokine receptor CCR2-binding motif (residues 13-35) of the monocyte chemoattractant protein-1 (MCP-1). Since monocytes are found concentrated in plaques prone to rupture, and our molecular imaging tool binds specifically to monocytes, this nanoparticle system may provide a noninvasive, detection system for plaques of high risk.
The MCP-1 peptide or Cy-7 was conjugated to DSPE-PEG-2000 and mixed to form self-assembled, fluorescently-labeled, monocyte-targeting peptide amphiphiles. The critical micelle concentration of MFPMs was determined to be approximately 1 μM with an average diameter of approximately 15 nm, confirmed via dynamic light scattering and transmission electron microscopy. Chemotaxis assays confirmed the chemoattractive capabilities of MFPMs using murine monocytes at 4 hours in vitro, and MFPMs were confirmed to be biocompatible using murine aortic endothelial cells and smooth muscle cells after 24 hours. Peptide amphiphile micelles can be synthesized with multiple functionality (i.e. targeting element, imaging dye, etc.) and our investigations will lay the ground work for peptide amphiphile micelle-mediated drug delivery at the site of vulnerable plaques.
- © 2013 by American Heart Association, Inc.