In vivo MRI detection of carotid atherosclerotic lesions and kidney inflammation in ApoE-deficient mice by using LOX-1 targeted iron nanoparticles

Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) plays a key role in atherosclerotic plaque initiation, formation and rupture, as well as in hyperlipidemia-induced glomerular disease. Here we report a sensitive, specific and biocompatible LOX-1-targeted-USPIO for the noninvasive MR imaging of LOX-1 within carotid atherosclerotic lesions and glomerular disease in apoE-deficient mice. In vitro analysis showed the highest uptake of targeted USPIOs in only activated RAW264.7 macrophages, and in vivo MRI studies showed signal loss in carotid atherosclerotic lesions after administration of targeted USPIOs at 8 h and 24 h. These areas of signal loss were correlated with the presence of nanoparticles in the atherosclerotic lesions, and immunohistochemistry and Perl’s staining confirmed the co-localization of the LOX-1/macrophages/MMP-9 and targeted nanoparticles. Finally, additional studies suggest that this targeted probe may have potential to noninvasively image early glomerular disease. This finding may provide important methods for characterizing vulnerable atherosclerotic plaques and hyperlipidemia-induced glomerular diseases.From the Clinical EditorA functionalized USPIO-based negative contrast material was used in this study, demonstrating feasibility of sensitive MRI-based detection of atherosclerotic plaque formation in the carotid arteries and in the renal cortex, paving the way to potential future clinical applications.

Graphical AbstractIn the current study, LOX-1-targeted-USPIO and untargeted USPIO have been synthesized and these USPIOs have been used in carotid atherosclerotic lesions model in apoE−/− mice which induced by non-constrictive polyethylene cuff implantation combined with 6-week high-fat diet. In vivo T2WI MRI studies showed signal loss in carotid atherosclerotic lesions after administration of targeted USPIOs at 8 h and 24 h. Furthermore, In vivo T2* MRI studies showed signal reduction in kidney cortex after administration of targeted USPIOs at 24 h. In addition, it showed limit signal reduction after untargeted-USPIO administration. This finding may provide important methods for characterizing vulnerable atherosclerotic plaques and hyperlipidemia-induced glomerular diseases.Figure optionsDownload high-quality image (241 K)Download as PowerPoint slide