Abstract
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.
Original language | English (US) |
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Pages (from-to) | 639-649 |
Number of pages | 11 |
Journal | Nanomedicine: Nanotechnology, Biology, and Medicine |
Volume | 10 |
Issue number | 3 |
DOIs | |
State | Published - Apr 2014 |
Externally published | Yes |
Keywords
- Atherosclerosis
- LOX-1
- Magnetic resonance imaging
- USPIO
ASJC Scopus subject areas
- Bioengineering
- Medicine (miscellaneous)
- Molecular Medicine
- Biomedical Engineering
- Materials Science(all)
- Pharmaceutical Science