MRI/optical dual-modality imaging of vulnerable atherosclerotic plaque with an osteopontin-targeted probe based on Fe3O4 nanoparticles

Abstract

Rupture of vulnerable atherosclerotic plaque is the major pathological cause of luminal thrombosis in acute coronary syndromes. Since foamy macrophages have been identified as a prominent component in vulnerable atherosclerotic lesions and osteopontin (OPN) is reported to be highly expressed in foamy macrophages, OPN could be a potential target for vulnerable atherosclerotic plaque imaging. The current study designed an OPN-specific MRI/optical dual-modality probe to detect vulnerable plaques. Fluorescence imaging revealed that 24 h after injection of the Cy5.5-OPN-DMSA-MNPs (COD-MNPs), the atherosclerotic plaques in carotid artery exhibited significant higher signals in high fat diet (HFD) fed mice in comparison to the group injected with Cy5.5-IgG-DMSA-MNPs (CID-MNPs) or normal diet fed group injected with COD-MNPs (1.87 ± 0.19 × 10¹⁰ vs. 0.74 ± 0.04 × 10¹⁰, 0.73 ± 0.03 × 10¹⁰ p/sec/cm²/sr, P < 0.05). Meanwhile, MRI displayed stronger T₂ contrast enhancement 24 h post-injection at the area of atherosclerotic plaques in the carotid of HFD fed group injected with COD-MNPs than group injected with CID-MNPs or normal diet fed group injected with COD-MNPs (post/pre signal ratio: 0.64 ± 0.04 vs. 0.95 ± 0.02, 0.98 ± 0.01, P < 0.05). As a dual-modality molecular probe, the resulting COD-MNPs conjugates exhibit promising potentials for noninvasive detection of vulnerable atherosclerotic plaque in vivo.

Keywords: Atherosclerotic plaques; Dual-modality molecular imaging; Macrophages; Nanoparticles.