Facile synthesis of superparamagnetic nickel-doped iron oxide nanoparticles as high-performance T1 contrast agents for magnetic resonance imaging

Small-sized iron oxide nanoparticles (IONPs) are an excellent alternative to clinical gadolinium-based contrast agents (GBCAs) in T1-weighted magnetic resonance imaging (MRI) due to their biosafety. However, their relaxation efficiency and contrast enhancement are not significant compared with those of GBCAs, and the nanomaterials face stability problems in vivo and difficulties in large-scale synthesis. Here, we designed and synthesized a series of 7 nm monodispersed biocompatible and superparamagnetic nickel-doped iron oxide nanoparticles (NiIO NPs) as safe contrast agents (CAs) for ultra-sensitive T1-weighted MR imaging. The nickel doping strategy transforms the iron oxide nanoparticles from traditional T2 CAs to T1 CAs. The Ni0.31Fe2.69O4 NPs exhibited a high longitudinal relaxivity (r1) of 9.1 mM-1 s-1, which is much higher than that of IONPs and 2.4 times that of clinical T1 CAs (Magnevist, 3.8 mM-1 s-1). NiIO NPs enable high-resolution T1-weighted and T2-weighted dual-mode MR imaging in vivo with long circulation time. These results, in hand with the excellent colloidal stability and superior biosafety, demonstrate the potential use of NiIO NPs for accurate diagnosis in deep-tissue T1-T2 dual-mode MR imaging.