Ultrasmall Ferrite Nanoparticles Synthesized via Dynamic Simultaneous Thermal Decomposition for High-Performance and Multifunctional T1 Magnetic Resonance Imaging Contrast Agent

Large-scale synthesis of monodisperse ultrasmall metal ferrite nanoparticles as well as understanding the correlations between chemical composition and MR signal enhancement is critical for developing next-generation, ultra-sensitive T-1 magnetic resonance imaging (MRI) nanoprobes. Herein, taking ultrasmall MnFe2O4 nanoparticles (UMFNPs) as a model system, we report a general dynamic simultaneous thermal decomposition (DSTD) strategy for controllable synthesis of monodisperse ultrasmall metal ferrite nanoparticles with sizes smaller than 4 nm. The comparison study revealed that the DSTD using the iron-eruciate paired with a metal-oleate precursor enabled a nucleation-doping process, which is crucial for particle size and distribution control of ultrasmall metal ferrite nano particles. The principle of DSTD synthesis has been further confirmed by synthesizing NiFe2O4 and CoFe2O4 nano particles with well-controlled sizes of similar to 3 nm. More significantly, the success in DSTD synthesis allows us to tune both MR and biochemical properties of magnetic iron oxide nanoprobes by adjusting their chemical composition. Beneficial from the Mn2+ dopant, the synthesized UMFNPs exhibited the highest r(1) relaxivity (up to 8.43 mM(-1) s(-1)) among the ferrite nanoparticles with similar sizes reported so far and demonstrated a multifunctional T-1 MR nanoprobe for in vivo high-resolution blood pool and liver-specific MRI simultaneously. Our study provides a general strategy to synthesize ultrasmall multicomponent magnetic nanoparticles, which offers possibilities for the chemical design of a highly sensitive ultrasmall magnetic nanoparticle based T-1 MRI probe for various clinical diagnosis applications.