MRI evaluation of atherosclerotic plaques targeted by iron nanoparticles linked with human antibody against oxidized low-density lipoprotein

Abstract

Objective To synthesize, characterize and test the efficacy of maghemite nanoparticles (MNPs) linked with antibodies against oxidized low-density lipoprotein(Ox-LDL) (anti-Ox-LDL-MNPs) and to evaluate its efficiency as in vivo MRI contrast agent in ApoE-/- mice. Methods Anti-human Ox-LDL monoclonal antibody and nonspecific IgG antibody were prepared by grafting antibody on the surface of 2,3-dimercaptosuccinnic acid (DMSA)-coated MNPs using the linker of (1-(3-dimethylaminopropyl)-3-ethylcarbodimide) hydrochloride(EDC). The morphology and activity of anti-Ox-LDL-MNPs were evaluated by transmission electron microscopy (TEM), and ELISA. ApoE-/- mice were divided into anti-Ox-LDL-MNPs group and IgG-MNPs group (n=5 in each group) and imaged at 7.0 T MR prior to contrast administration and 24 h after injection of 30 mg Fe/kg. MRI was performed using black-blood T2 weighted multi-spin multi-echo sequence. Prussian blue, CD68 and Ox-LDL immunohistological stains were undertaken for the detection of iron, macrophages and Ox-LDL in excised mouse aorta. Paired t test was used to analyze the data. Results Anti-Ox-LDL-MNPs or IgG-MNPs had similar hydrated diameters ((21.5±3.3) nm and (22.3±4.1) nm). Significant modulation of the MR signal was observed with anti-Ox-LDL-MNPs (20.89±1.50 vs 7.30±1.19; t=5.373, P 0.05). Immunohistochemistry confirmed the co-localization of the macrophages and iron oxide nanoparticles after anti-Ox-LDL-MNPs administration. Conclusions Ox-LDL targeting MNPs nanoparticles may be used to directly detect Ox-LDL and image atherosclerotic lesions within 24 h after nanoparticle administration. It may be a strategy for the evaluation of atherosclerotic plaques in vivo. Key words: Atherosclerosis; Magnetic resonance imaging; Nanotechnology; Lipoproteins, LDL; Mice