With the goal of exploring strategies for detection, prevention, and treatment of atherosclerosis, we propose using peptide amphiphile (PA) molecules as building blocks for novel diagnostic and therapeutic systems. Peptide amphiphiles are formed by conjugating a hydrophobic lipid tail to a hydrophilic head group containing a targeting peptide of interest. For this work, the peptide used is CREKA, a five amino acid peptide, which has been shown to target fibrin, a marker of late stage atherosclerotic plaques. In aqueous conditions, the hydrophobic interactions of the tails drive PAs to self assemble into hierarchically ordered structures including spherical micelles. Previously, our group has shown that these CREKA peptide amphiphile micelles accumulate, at plaques in ApoE knockout mice. While we continue to explore CREKA as a peptide for targeting late stage atherosclerotic plaques, recent investigations also include the exploration of early stage, atherosclerotic molecular targets for our micelles, such as MCP-1 and VCAM-1. Since peptide amphiphile micelles are a modular vehicle that allows for incorporation of multiple targeting and therapeutic peptides, and the hydrophobic core provides a means of delivery for hydrophobic drugs, we aim to deliver a drug of interest as well as imaging agents that will enable us to detect the progression of atherosclerosis.
Fluorescencently-labeled, CREKA peptide amphiphile micelles bind specifically to plaques of the aortic tree in late stage ApoE knock out mice as shown A) qualitatively and B) quantitatively. Image taken from Peters et al., PNAS, 106 9815-9819 (2009).