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LOX-1-Targeted Iron Oxide Nanoparticles Detect Early Diabetic Nephropathy in db/db Mice
Bing Luo1, Song Wen1, Yu-Chen Chen1
1Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, Jiangsu, 210009, China.
Purpose:
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.
Procedures:
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.
Results:
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.
Conclusions:
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.
