Improved in vivo detection of atherosclerotic plaques with a tissue factor-targeting magnetic nanoprobe

Abstract

Rupture of atherosclerotic plaques causes acute cardiovascular and cerebrovascular pathology. Tissue factor (TF) is a key factor that affects the development of atherosclerotic plaques and the formation of thrombus and thus constitutes a potential target for the detection of atherosclerotic plaques. In this study, the conjugation of the fusion protein 'enhanced green fluorescent protein with the first epidermal growth factor domain' (EGFP-EGF1) and superparamagnetic iron oxide nanoparticles (EGFP-EGF1-SPIONs) was explored for molecular imaging of TF-positive atherosclerotic plaques. EGFP-EGF1-SPIONs showed improved accuracy, superior contrast effects, and better cytocompatibility compared with common contrast agents in the detection of atherosclerotic plaques of apolipoprotein E knockout (ApoE^-/-) mice using magnetic resonance imaging. In conclusion, EGFP-EGF1-SPION is a promising TF-targeting nanoprobe to precisely and specifically detect atherosclerotic plaques, which may improve molecular imaging diagnosis of cardiovascular and cerebrovascular events for the comprehensive evaluation of atherosclerosis. STATEMENT OF SIGNIFICANCE: Traditional methods can only display the status of atherosclerosis, but not forecast the progress of lesions efficiently. It remains challenging to evaluate the plaques specifically and sensitively. In this study, we constructed a tissue factor-targeted magnetic nanoprobe to specifically detect plaques by magnetic resonance imaging in vivo, which will improve the diagnostic technology for atherosclerotic plaques and offer molecular level guidance to treat atherosclerosis. Furthermore, this strategy has critical clinical significance on prevention, diagnosis and therapeutic evaluation of cardio-cerebral vascular events.

Keywords: Atherosclerotic plaque; EGFP-EGF1; Magnetic resonance imaging; Superparamagnetic iron oxide nanoparticle; Tissue factor.