Abstract
IgA nephropathy is the most common glomerular disease in the world and has become a serious threat to human health. Accurate and non-invasive molecular imaging to detect and recognize the IgA nephropathy is critical for the subsequent timely treatment; otherwise, it may progress to end-stage renal disease and lead to glomerular dysfunction. In this study, we have developed a sensitive, specific, and biocompatible integrin αvβ3-targeted superparamagnetic Fe3O4 nanoparticles (NPs) for the noninvasive magnetic resonance imaging (MRI) of integrin αvβ3, which is overexpressed in glomerular mesangial region of IgA nephropathy. The rat model of IgA nephropathy was successfully established and verified by biochemical tests and histological staining. Meanwhile, the clinical 18F-AlF-NOTA-PRGD2 probe molecule was utilized to visualize and further confirmed the IgA nephropathy in vivo via positron emission computed tomography. Subsequently, the Fe3O4 NPs were conjugated with arginine–glycine–aspartic acid (RGD) molecules (Fe3O4-RGD), and their integrin αvβ3-targeted T2-weighted imaging (T2WI) potential has been carefully evaluated. The Fe3O4-RGD demonstrated great relaxation in vivo. The T2WI signal of renal layers in the targeted group at 3 h after intravenous injection of Fe3O4-RGD was distinctly lower than baseline, indicating MRI signal decreased in the established IgA nephropathy rat model. Moreover, the TEM characterization and Prussian blue staining confirmed that the Fe3O4-RGD was located at the region of glomerulus and tubular interstitium. Moreover, no obvious signal decreased was detected in the untargeted Fe3O4 treated and normal groups. Collectively, our results establish the possibility of Fe3O4-RGD serving as a feasible MRI agent for the noninvasive diagnosis of IgA nephropathy.
Highlights
IgA nephropathy is the most common glomerular disease in the world, and approximately 50% of IgA nephropathy will progress to end-stage renal disease within 30 years regardless of treatment (Moriyama et al, 2014)
The morphology and structure were investigated by transmission electron microscopy (TEM)
There were electron-dense deposits in the glomerular mesangial area in the model group under TEM image, while no electron-dense deposits were seen in the normal group. These results indicated that model rats presented an increase in glomerular mesangial cells, mesangial matrix, and immune deposits, corresponding to the pathological changes of IgA nephropathy depicted in the literature (Caliskan and Kiryluk, 2014), and preliminarily demonstrated that the animal model was successfully constructed
Summary
IgA nephropathy is the most common glomerular disease in the world, and approximately 50% of IgA nephropathy will progress to end-stage renal disease within 30 years regardless of treatment (Moriyama et al, 2014). Magnetic resonance imaging (MRI), as a common examination for clinical disease diagnosis, possesses high spatial resolution and good tissue contrast and is not radioactive (Ye et al, 2002; Jiang et al, 2009). A facile method was used to prepare the uniform BSA-modified Fe3O4 nanoparticles (NPs) These paramagnetic NPs were functionalized with RGD molecules (RGD-Fe3O4) as an integrin αvβ3targeting MRI nanoprobe to recognize the glomerular mesangial region of IgA nephropathy (Scheme 1). Weighted imaging (T2WI) RGD-Fe3O4 NPs have been carefully evaluated in the IgA nephropathy rat model. Our study provided a foundation into the development of safe and effective T2WI for molecular imaging of detecting IgA nephropathy noninvasively
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