Ultrasmall Fe3O4 and Gd2O3 hybrid nanoparticles for T1-weighted MR imaging of cancer

Abstract

Abstract Gadolinium-based contrast agents (GdCAs) have been the most frequently used T1-weighted magnetic resonance imaging (MRI) contrast agents for decades. However, they have serious disadvantages such as low longitudinal relaxivity value (r1) and high dose associated-nephrotoxicity that restrict their wide applications. These emphasize the need for an ideal stable and biocompatible T1-weighted CA with high contrast enhancement performance. Here, we propose a wet-chemical synthesis technique to form a nanocomposite consisting of ultrasmall iron oxide nanoparticles (US-IO) and Gd2O3 hybrid nanoparticles stabilized with dextran (FG-HNPs) for T1-weighted MR imaging. Relaxometry study showed that FG-HNPs have a high r1 value (42.28 mM− 1S− 1) and low relaxivity ratio (r2/r1: 1.416) at 3.0 T. In vivo MRI contrast enhancement factor (ΔSNR) for FG-HNPs (257.025 ± 17.4%) was found to be 1.99-fold higher than US-IO (129.102 ± 15%) and 3.35-fold higher than Dotarem (76.71 ± 14.2%) as routinely-used T1-weighted CA. The cytotoxicity assay and histological examination confirmed the biocompatibility of FG-HNPs. The biodistribution study, transmission electron microscopy (TEM) and Prussian blue (PB) staining of tumor tissue proved the effective tumor localization of FG-HNPs. Therefore, FG-HNPs can be suggested as a promising CA for T1-weighted MRI of tumors by virtue of their remarkable relaxivities and high biocompatibility.