Size-controlled synthesis of superparamagnetic iron oxide nanoparticles and their surface coating by gold for biomedical applications

The size mono-dispersity, saturation magnetization, and surface chemistry of magnetic nanoparticles (NPs) are recognized as critical factors for efficient biomedical applications. Here, we performed modified water-in-oil inverse nano-emulsion procedure for preparation of stable colloidal superparamagnetic iron oxide NPs (SPIONs) with high saturation magnetization. To achieve mono-dispersed SPIONs, optimization process was probed on several important factors including molar ratio of iron salts [Fe3+ and Fe2+], the concentration of ammonium hydroxide as reducing agent, and molar ratio of water to surfactant. The biocompatibility of the obtained NPs, at various concentrations, was evaluated via MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and the results showed that the NPs were non-toxic at concentrations <0.1 mg/mL. Surface functionalization was performed by conformal coating of the NPs with a thin shell of gold (∼4 nm) through chemical reduction of attached gold salts at the surface of the SPIONs. The Fe3O4 core/Au shell particles demonstrate strong plasmon resonance absorption and can be separated from solution using an external magnetic field. Experimental data from both physical and chemical determinations of the changes in particle size, surface plasmon resonance optical band, phase components, core–shell surface composition, and magnetic properties have confirmed the formation of the mono-dispersed core–shell nanostructure.

► Increasing the concentration of iron salts, cubic-shape SPION NPs were formed. The magnetic saturation of the SPIONs was also increased.
► The concentration of reducing agent exhibited marginal effect on the size of SPIONs but influenced the crystallinity of the NPs. A lower magnetic saturation was obtained at higher NH4OH concentrations.
► Mono-dispersed SPIONs can be prepared by nano-emulsion procedure at w=23, [Fe]=2.12 M, and [NH4OH]=30%. Under this condition, NPs with dimension of 9±3 nm and magnetic saturation of 54 emu/g are obtained. The synthesized SPIONs exhibited acceptable biocompatibility, >80% viability after 24 h incubation in L929 cells at concentrations <0.1 mg/mL.
► Conformal coating of SPIONs by a gold shell (∼4 nm) was performed and confirmed by various analytical techniques including, TEM, SPR, XRD, and XPS. VSM study showed a decrease in the magnetic saturation in expense of an increase in the coercivity due to the non-magnetic nature of the shell and coarser NPs. In spite of that, the presence of gold favours immobilization of affinity ligands on the surface of SPIONs for biomedical applications.