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

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Summary

Introduction

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.

Results
Conclusion

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