Optimizing the silanization of thermally-decomposed iron oxide nanoparticles for efficient aqueous phase transfer and MRI applications

Abstract

The design of magnetic iron oxide nanoparticles (IONPs) as contrast agents for magnetic resonance imaging (MRI) requires good magnetic properties of the core but also an organic coating suitable for in vivo applications. IONPs synthesised by thermal decomposition display optimal properties due to their excellent monodispersity, controlled morphology and high crystallinity; however, their in situ coating by hydrophobic ligands make them only dispersible in nonpolar solvents. A wide range of methods was developed to coat IONPs with molecules or polymers bearing anchoring groups such as carboxylates mainly. Nonetheless, very few have dealt with silane based molecules due to difficulties (e.g., slow kinetics of reaction, NPs aggregation during reaction, non miscibility of solvents) to graft homogeneously and efficiently silanes at the surface of hydrophobic NPs. In this work, a new and versatile method was developed to graft hydrophilic silanes on the surface of hydrophobic IONPs based on the direct reaction of IONPs in miscible polar/apolar co-solvents: EtOH/CHCl₃. The feasibility of this efficient process was demonstrated by using various silanes bearing amino and carboxylate end-groups. We show that this novel process allows several improvements in comparison with the few existing methods to silanize hydrophobic IONPs: (i) shorter reaction time, (ii) increased amount of processed NPs per cycle, (iii) the establishment of a silane limit stoichiometry to ensure good colloidal properties and (iv) easier implementation without the need of specific or stringent treatments, which are all key issues for scale-up aspects. IONPs grafted with aminosilanes display an excellent colloidal stability in ethanol and only in acidic aqueous solutions (pH < 5). By contrast, carboxylated silane-IONPs were shown to exhibit excellent colloidal stability in the physiological pH range (pH = 6–8). Moreover, such new silanized NPs display MRI contrast enhancement as efficient as commercially available magnetic NPs.