A sub-50-nm monosized superparamagnetic Fe₃O ₄@SiO₂ T₂-weighted MRI contrast agent: Highly reproducible synthesis of uniform single-loaded core-shell nanostructures

Oleic acid stabilized superparamagnetic iron oxide nanoparticles (SPION) were selected as the cores for fabrication of sub-50-nm monodisperse single-loaded SPION@SiO₂ core-shell nanostructures. Parameters that influence the formation of SPION@SiO₂ in the water-in-oil reverse microemulsion system have been systematically investigated. The sufficiently high concentration of well-dispersed SPION, together with an appropriately low injection rate of tetraethoxysilane, were found to be the keys to efficiently prevent the homogeneous nucleation of silica and obtain a high-quality singleloaded core-shell nanocomposite. A more detailed mechanism for incorporating oleic acid capped inorganic functional nanoparticles into silica is proposed on the basis of previous reports and our new experimental results. Finally, the as-synthesized SPION@SiO₂ nanospheres are exploited as an MRIenhanced contrast agent, and their contrast effect in solution is tested by using a clinical MRI instrument.