Citrate coated iron oxide nanoparticles with enhanced relaxivity for in vivo magnetic resonance imaging of liver fibrosis

Superparamagnetic iron oxide nanoparticles are widely used for the magnetic resonance imaging (MRI) applications. The surface characteristics, magnetic properties, size and targeting efficiency of the material are crucial factors for using the same as contrast agents. We report a simple synthesis method of citrate coated iron oxide nanoparticles and its systematic characterization. The developed system is highly water dispersible with an average particle size of 12 nm. The particles in water are monodisperse and are found to be stable over long periods. The efficiency of the material to de-phase water proton has been studied for various concentrations of iron using longitudinal (T1) and transverse (T2) weighted MRI. The coating thickness of the nanoparticle was optimized so that they exhibited a high transverse to longitudinal relaxivity (r2/r1) ratio of 37.92. A clear dose-dependent contrast enhancement was observed in T2 weighted in vivo MR imaging of liver fibrosis model in rodents. The labelling efficacy of the particle and the intracellular magnetic relaxivity were also investigated and presented. The particles were also tested for blood and cellular compatibility studies. Development of fibrosis and presence of iron in the liver was confirmed by histopathological analysis. From this study, we conclude that the citrate coated ultra small superparamagnetic iron oxide nanoparticles (C-USPION) with optimized parameters like particle size and magnetic property are capable of producing good MR contrast in imaging of liver diseases.