(385c) Peptide-Functionalized Superparamagnetic Iron Oxide Nanoparticles for Diagnosis and Treatment of Atherosclerosis

Atherosclerosis is one of the major causes of cardiovascular disease, which remains the leading cause of death in the United States.  The development and progression of atherosclerosis varies on a case-by-case basis, but certain universal markers exist which provide a means for a targeted approach to diagnosing and treating the disease.  Magnetic particle imaging (MPI), an emerging new imaging technology with excellent contrast and no ionizing radiation, is being investigated for its potential use in imaging of atherosclerotic plaques.  Through the use of iron oxide nanoparticles, MPI can be used to quantify the amount of contrast agent delivered to atherosclerotic plaques, thereby providing a diagnostic metric to assess the progression of the disease.   

To this end, we are functionalizing iron oxide particles with peptide targeting agents via 2-pyridyl disulfide. Functionalization of the cysteine residue in the peptide CREKA and CGGGKGRGDSP with 2-pyridyl disulfide provides a means of quantifying the average number of peptides per particle¹.  Preliminary work has shown the ability of CREKA to selectively target fibrin at the areas most prone to rupture, namely the plaque corners².  Iron oxide nanoparticles functionalized with CREKA can potentially be used to image the extent of occlusion of the plaque in a given artery using magnetic particle imaging.  Infrared spectroscopy confirmed successful conjugation of the peptide to iron oxide nanoparticles.  Transmission electron microscopy images and dynamic light scattering show that individual particles smaller than 40 nm in diameter are formed.  To provide proof of principle in vitro, conjugation of the GRGDSP peptide, which has previously been used for its cell adhesion properties, is currently being explored to test the ability of magnetic particle imaging to detect peptide-functionalized iron oxide particles attached to the cell exterior.  Initial 2D MPI scans using peptide-functionalized iron oxide particles associated with cells provide evidence not only for the ability to image contrast agent while associated to cells, but also the potential specificity provided by peptide functionalization.  Successful detection of RGD-conjugated iron oxide nanoparticles will pave the way for future in vivo imaging studies using CREKA in conjunction with magnetic particle imaging to detect atherosclerotic plaques. 

[1] Josephson, L, et al. High-Efficiency Intracellular Magnetic Labeling with Novel Superparamagnetic-Tat Peptide Conjugates. Bioconjugate Chem. 1999; 10: 510-520.

[2] Peters, D, et al. Targeting Atherosclerosis by Using Modular Multifunctional Micelles. PNAS. 2009; 106: 9815-9819.