Optimization of the Synthesis of Superparamagnetic Contrast Agents by the Design of Experiments Method

The synthesis of iron oxide nanoparticles by coprecipitation of ferrous and ferric ions was optimized in aqueous and organic medium. For both syntheses, the influence of different factors on the nanoparticle size was successfully evaluated by the "design of experiments" method. This methodology allows finding in very few runs the optimal experimental conditions to synthesize nanoparticles with a predetermined radius. Aqueous and organic syntheses of magnetite seem to be complementary. The first one leads to smaller magnetite nanoparticles (with radius comprised between 4.9 and 5.7 nm). These particles were stabilized by electrostatic repulsion through a two-step process and needed an additional coating. Conversely, the synthesis in organic medium allows producing, in one step, magnetite nanoparticles embedded within a silica corona. In this protocol, the Ostwald ripening phenomenon seems to play a very important role in the formation of larger magnetite crystals (with radius comprised between 4.8 and 7.7 nm) as well as in the control of their monodispersity. The newly synthesized nanoparticles and the experimental protocol used to produce them have a great potential for future applications in molecular MR imaging, cellular MR imaging, and thermotherapy.