Imaging atherosclerotic plaques in vivo using peptide-functionalized iron oxide nanoparticles

Two peptides that bind to markers of atherosclerotic plaques are currently under investigation. The first peptide is RGD, which binds to α_vβ₃, an integrin overexpressed on endothelial cells present at the plaque and macrophages that infiltrate the plaque ¹. CREKA, a five amino acid peptide that binds to fibrin², a marker of late stage plaque development, is also used to functionalize the SPIOs. In order to evaluate the efficacy of the RGD-functionalized iron oxide particles, a carotid ligation mouse model which results in macrophage-rich atherosclerotic lesions is currently being used. The carotid ligation model simulates the inflammation markers present in the development of atherosclerotic plaques, whereby one carotid is ligated and the other carotid is left untouched as an internal control. In addition, CREKA-functionalized iron oxide particles have been explored with ApoE knockout mice. These mice are genetically engineered to develop plaques with analogous markers to those that develop in humans. Peptide-functionalized SPIOs were injected at a concentration of 24 mg Fe/kg. 48 hours after injection, an MRI of the mice is obtained on a whole-body 3T MRI scanner (Signa HDx, GE Healthcare). After sacrifice, the mice undergo Magnetic Particle Imaging (Field Free Line scanner with 2.35 T/m selection field) to compare to the MRI. Figure 1 shows an MRI obtained both pre-injection (a) and post-injection (b) with CREKA-functionalized SPIOs. Preliminary results show a small accumulation of iron oxide particles in the aorta using the CREKA-functionalized SPIOs and ApoE knockout mice. Histology shows that excess SPIOs accumulated in the liver, as expected.