LOX-1-Targeted Iron Oxide Nanoparticles Detect Early Diabetic Nephropathy in db/db Mice

作者:Luo, Bing; Wen, Song; Chen, Yu-Chen; Cui, Ying; Gao, Fa-Bao; Yao, Yu-Yu; Ju, Sheng-Hong; Teng, Gao-Jun*
来源:Molecular Imaging and Biology, 2015, 17(5): 652-660.
DOI:10.1007/s11307-015-0829-5

摘要

Activation of the low-density lipoprotein receptor 1 (LOX-1) contributes to pervasive inflammation in early diabetic nephropathy (DN). This study determined the feasibility of anti-LOX-1-ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) for noninvasive detection of inflammatory renal lesions in early DN. @@@ Anti-mouse LOX-1 antibody was conjugated to polyethyleneglycol-coated USPIOs. In vitro analysis of USPIOs uptake was performed in RAW264.7 macrophages. DN and control mice were imaged by MRI prior to and 24 h after contrast treatment. @@@ Anti-LOX-1 USPIOs were selectively taken up by macrophages, and kidney T2* MRI showed a lower signal intensity in the cortex of DN mice after 24 h administration of anti-LOX-1 USPIOs. Positive Perl's staining in DN lesions, indicating the presence of iron oxide, was consistent with immunohistochemistry indicating the presence of LOX-1 and CD68. @@@ This report shows that anti-LOX-1 USPIOs detect LOX-1-enriched inflammatory renal lesions in early DN mice. Our study provides important information for characterizing and monitoring early DN.