Visualization of Vascular Inflammation in the Atherosclerotic Mouse by Ultrasmall Superparamagnetic Iron Oxide Vascular Cell Adhesion Molecule-1–Specific Nanoparticles

作者：Marta Michalska, Lina H. Machtoub, Helga D. Manthey, Elisabeth Bauer, Volker Herold, Georg Krohne, Gunthard Lykowsky, Markus F. Hildenbrand, Thomas Kampf, Peter M. Jakob, Alma Zernecke, Wolfgang R. Bauer · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2012 · DOI：10.1161/atvbaha.112.255224 · 被引用次数：77 · 研究领域：Nanoparticle-Based Drug Delivery、Characterization and Applications of Magnetic Nanoparticles、Spectroscopy Techniques in Biomedical and Chemical Research

OBJECTIVE: Noninvasive imaging of atherosclerosis remains challenging in clinical applications. Here, we applied noninvasive molecular imaging to detect vascular cell adhesion molecule-1 in early and advanced atherosclerotic lesions of apolipoprotein E-deficient mice. METHODS AND RESULTS: Ultrasmall superparamagnetic iron oxide particles functionalized with (P03011) or without (P3007) vascular cell adhesion molecule-1-binding peptide were visualized by ultra high-field (17.6 T) magnetic resonance. Injection of P03011 resulted in a marked signal loss in the aortic root of apolipoprotein E-deficient mice fed a Western diet for 8 and 26 weeks in vivo and ex vivo, compared with preinjection measurements, P3007-injected mice, and P03011- or P3007-injected age-matched C57BL/6 controls. Histological analyses revealed iron accumulations in the intima, in colocalization with vascular cell adhesion molecule-1-expressing macrophages and endothelial cells. Coherent anti-Stokes Raman scattering microscopy demonstrated iron signals in the intima and media of the aortic root in the P03011-injected but not untreated apolipoprotein E-deficient mice, localized to macrophages, luminal endothelial-like cells, and medial regions containing smooth muscle cells. Electron microscopy confirmed iron particles enclosed in endothelial cells and in the vicinity of smooth muscle cells. CONCLUSIONS: Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of apply...