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

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-dimelhylaminopropyl)-3-ethyl-carbodimide) 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 multiecho 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 < 0.01), minor MR signal modulation was observed following administration of IgG-MNPs (20.84 ± 5.47 vs 18.66 ± 2.84; t = 2.620, 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. (authors)