Abstract
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.
Highlights
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
The results show that the anti-OxLDL-ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles has excellent diagnostic ability as an MRI contrast agent, suggesting further potential for characterizing carotid atherosclerotic lesions
To assess the stability of the targeted and untargeted USPIO nanoparticles, the hydrodynamic size of the USPIO nanoparticles in PBS or 10% FBS was analyzed by dynamic light scattering (DLS) measurement within 24 h
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. PEG-coated USPIO nanoparticles with polyclonal rabbit anti-copper-oxide mouse LDL antibody were developed to generate a novel, targeted MRI contrast agent. These nanoparticles were used to detect plaques in an in vivo perivascular collar-induced atherosclerotic lesion model in carotid arteries of apoEϪ/Ϫ mice.
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