Magnetic resonance imaging of macrophage activity in atherosclerotic plaques of apolipoprotein E-deficient mice by using polyethylene glycolated magnetic fluorescent silica-coated nanoparticles

We have recently synthesized organic dye-incorporated silica-coated core-shell magnetic nanoparticles (MFSNs) that enable the detection of both fluorescence and magnetic properties in cells and tissues by using magnetic resonance imaging (MRI). Furthermore, polyethylene glycolation of the surface of these MFSNs would render them more stable and biocompatible, and thus allow their in vivo use as a circulating agent with a long half-life. Atherosclerotic vascular diseases are the leading cause of death worldwide. A noninvasive diagnostic imaging method is required to identify vulnerable plaques prior to the occurrence of a clinical event. Macrophages are the key cellular mediators in the pathogenesis of plaque inflammation and vulnerability. We evaluated whether the use of polyethylene glycolated (PEGylated) MFSNs could help in effectively detecting the macrophage activity in the aorta of apolipoprotein E (apoE)-deficient mice. PEGylated MFSNs (Fe, 30 mg/kg) were injected via the tail vein in 1.2% cholesterol-fed 30-week-old apoE-deficient mice. After 24 h, ex vivo MRI was carried out. The atheromas were then observed by confocal laser scanning microscopy (CLSM), and immunohistochemical staining targeted toward the macrophages was performed. Ex vivo MRI demonstrated robust enhancement of the atherosclerotic plaques along the aortic wall. CLSM images showed accumulation of PEGylated MFSNs in the atherosclerotic plaques, and histological examination revealed the localization of MFSNs in the macrophages present in the lesion. Therefore, PEGylated MFSNs could function as an effective multimodal imaging agent in the identification of macrophage activity in atherosclerotic plaques.