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 NaGdF:Yb,Er@NaGdF 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.
Aims: This study aims to explore non-invasive imaging of atherosclerotic plaque through magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) by using profilin-1 targeted magnetic iron oxide nanoparticles (PF1-Cy5.5-DMSA-Fe3O4-NPs, denoted as PC-NPs) as multimodality molecular imaging probe in murine model of atherosclerosis. Methods and Results: PC-NPs were constructed by conjugating polyclonal profilin-1 antibody and NHS-Cy5.5 fluorescent dye to the surface of DMSA-Fe3O4-nanoparticles via condensation reaction. Murine atherosclerosis model was induced in apoE-/- mice by high fat and cholesterol diet (HFD) for 16 weeks. The plaque areas in aortic artery were detected with Oil Red O staining. Immunofluorescent staining and Western blot analysis were applied respectively to investigate profilin-1 expression. CCK-8 assay and transwell migration experiment were performed to detect vascular smooth muscle cells (VSMCs) proliferation. In vivo MRI and NIRF imaging of atherosclerotic plaque were carried out before and 36 h after intravenous injection of PC-NPs. Oil Red O staining showed that the plaque area was significantly increased in HFD group (p<0.05). Immunofluorescence staining revealed that profilin-1 protein was highly abundant within plaque in HFD group and co-localized with α-smooth muscle actin. Profilin-1 siRNA intervention could inhibit VSMCs proliferation and migration elicited by ox-LDL (p<0.05). In vivo MRI and NIRF imaging revealed that PC-NPs accumulated in atherosclerotic plaque of carotid artery. There was a good correlation between the signals of MRI and ex vivo fluorescence intensities of NIRF imaging in animals with PC-NPs injection. Conclusion: PC-NPs is a promising dual modality imaging probe, which may improve molecular diagnosis of plaque characteristics and evaluation of pharmaceutical interventions for atherosclerosis.
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