OxLDL-targeted iron oxide nanoparticles for in vivo MRI detection of perivascular carotid collar induced atherosclerotic lesions in ApoE-deficient mice

Atherosclerotic disease is a leading cause of morbidity and mortality in developed countries, and oxidized LDL (OxLDL) plays a key role in the formation, rupture, and subsequent thrombus formation in atherosclerotic plaques. In the current study, anti-mouse OxLDL polyclonal antibody and nonspecific...

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Bibliographic Details
Published in:	Journal of lipid research Vol. 53; no. 5; pp. 829 - 838
Main Authors:	Wen (文颂), Song, Liu (柳东芳), Dong-Fang, Liu (刘振), Zhen, Harris, Steven, Yao (姚玉宇), Yu-Yu, Ding (丁琪), Qi, Nie (聂芳), Fang, Lu (卢瞳), Tong, Chen (陈华俊), Hua-Jun, An (安艳丽), Yan-Li, Zang (臧凤超), Feng-Chao, Teng (滕皋军), Gao-Jun
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-05-2012 The American Society for Biochemistry and Molecular Biology Elsevier
Subjects:	Animals Apolipoproteins E - deficiency atherosclerosis Carotid Arteries Constriction Contrast Media - chemistry Contrast Media - metabolism Ferric Compounds - chemistry Ferric Compounds - metabolism Lipoproteins, LDL - metabolism low density lipoprotein magnetic resonance imaging Magnetic Resonance Imaging - methods Male Mice Mice, Inbred C57BL molecular imaging Nanoparticles Plaque, Atherosclerotic - diagnosis Plaque, Atherosclerotic - etiology Plaque, Atherosclerotic - metabolism Polyethylene Glycols - chemistry atherosclerosis magnetic resonance imaging low density lipoprotein molecular imaging
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Summary:	Atherosclerotic disease is a leading cause of morbidity and mortality in developed countries, and oxidized LDL (OxLDL) plays a key role in the formation, rupture, and subsequent thrombus formation in atherosclerotic plaques. In the current study, anti-mouse OxLDL polyclonal antibody and nonspecific IgG antibody were conjugated to polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, and a carotid perivascular collar model in apolipoprotein E-deficient mice was imaged at 7.0 Tesla MRI before contrast administration and at 8 h and 24 h after injection of 30 mg Fe/kg. The results showed MRI signal loss in the carotid atherosclerotic lesions after administration of targeted anti-OxLDL-USPIO at 8 h and 24 h, which is consistent with the presence of the nanoparticles in the lesions. Immunohistochemistry confirmed the colocalization of the OxLDL/macrophages and iron oxide nanoparticles. The nonspecific IgG-USPIO, unconjugated USPIO nanoparticles, and competitive inhibition groups had limited signal changes (p < 0.05). This report shows that anti-OxLDL-USPIO nanoparticles can be used to directly detect OxLDL and image atherosclerotic lesions within 24 h of nanoparticle administration and suggests a strategy for the therapeutic evaluation of atherosclerotic plaques in vivo.
ISSN:	0022-2275 1539-7262
DOI:	10.1194/jlr.M018895