Evaluation of polyol-made Gd3+-substituted Co0.6Zn0.4Fe2O4 nanoparticles as high magnetization MRI negative contrast agents

The structural, microstructural, and magnetic properties of ~5-nm-sized Co_0.6Zn_0.4Fe_2 − xGd_xO₄ nanoparticles were investigated in order to evaluate their capability to enhance the magnetic resonance imaging contrast as high magnetization agents. A focus was made on the solubility of Gd³⁺ cations within the spinel lattice. By coupling X-ray diffraction to X-ray fluorescence spectroscopy, we demonstrated that only a limited fraction of Gd³⁺ can substitute Fe³⁺ ions into the whole crystal structure and does not exceed 6 at.-%. At this concentration, the room temperature (27°C) saturation magnetizations of the prepared superparamagnetic nanocrystals were found to be close to 80 emu g⁻¹. Coating these nanoparticles with hydrophilic dopamine ligands leads to the formation of ~50-nm-sized clusters in water. As a consequence, relatively high r₂/r₁ ratios of transverse to longitudinal proton relaxivities and high r₂ values were measured in the resulting colloids at physiological temperature (37°C) for an applied magnetic field of 1.41 T: 33 and 188 mM⁻¹ sec⁻¹, respectively, for the richest system in gadolinium. Moreover, after incubation with healthy human model cells (fibroblasts) at doses as high as 10 μg mL⁻¹, they induce neither cellular death nor acute cellular damage making the engineered probes particularly valuable for negative magnetic resonance imaging contrasting.