Molecular Imaging of Vulnerable Atherosclerotic Plaques in Vivo with Osteopontin-Specific Upconversion Nanoprobes

Owing to the high mortality rate of cardiovascular diseases, developing novel noninvasive diagnostic methods becomes urgent and mandatory. It is well-known that the rupture of vulnerable plaques directly leads to deadly consequences. However, differentiating vulnerable plaques from stable plaques remains challenging in the clinic. In the current study, osteopontin (OPN), a secreted biomarker associated with macrophages and foamy macrophages, was selected as a target for identifying the vulnerable plaques. A dual modality imaging probe was constructed by covalently attaching an OPN antibody to NaGdF₄:Yb,Er@NaGdF₄ upconversion nanoparticles. Upon intravenous injection of the resulting probes, upconversion optical imaging was performed to visualize the plaques induced by altering the shear stress in carotid arteries of a mouse model. The imaging studies revealed that the signals of vulnerable and stable plagues induced by lowered shear stress and oscillatory shear stress, respectively, presented significantly different signal intensities, implying that the current probe and imaging strategy are potentially useful for a precise diagnosis of atherosclerosis plaques.