Mannose-conjugated Ferritin Nanocages for Targeted MRI of Atherosclerosis

Atherosclerosis is characterized by the recruitment of monocytes to the subendothelial space which then mature into macrophages in the presence of macrophage colony stimulating factors and under the influence of their microenvironment to either M1 or M2 phenotypes. Early detection of atherosclerosis is challenged by a phenomenon known as positive arterial remodelling. This phenomenon is characterized by outward expansion of arterial walls in response to development of plaques, thus retaining the lumen diameter and demonstrating no stenosis. It is one of the major causes for missing out the detection of atherosclerosis by techniques that rely on lumenography. This leads to the need for imaging agents capable of targeting and imaging plaque components. The current study aims at targeting one such plaque component, the M2 macrophages, that are prevalent in higher numbers during early-stage atherosclerosis and to image these macrophages using magnetic resonance imaging (MRI) to aid early detection and facilitate timely therapeutic intervention of atherosclerosis. The study employs ferritin, an iron storage protein, with its natural ligand, iron, for MRI contrast. M2 macrophages are known to express mannose receptors on their surface, and we thus aim at using mannose conjugated ferritin nanocages for targeted MRI of the M2 macrophages in the atherosclerotic plaques. Mannose-conjugation is hypothesized to increase accumulation of ferritin nanocages in M2 macrophages and therefore improve contrast by virtue of targeting.