Zn2+ and Mn2+ doping effect on spin dynamics of Fe3O4-based magnetic nanoparticles: A possible path to efficient MRI contrast agents

Iron oxide-based magnetic nanoparticles (MNPs) play a major role as contrast agents for magnetic resonance imaging (MRI). The introduction of Zn2+ and Mn2+ ions within their crystal lattice alters the magnetic anisotropy and the spin dynamical properties of the systems, which in turn influence the nuclear relaxation mechanisms that drive contrast enhancement in MRI. This work explored two sets of doped-magnetite MNPs (chemical formula ZnxMnyFe3-x-yO4) with core diameters of d 4 or 15 nm produced by the fast and reproducible microwave-assisted synthesis method, and using different solvents like water or polyols. The d 4 nm MNPs were doped with Zn2+, from x=0 to 0.9; for Zn2+=0.5, Mn^2+ was introduced at y=0.2,0.4. The d 15 nm MNPs were doped with Zn2+ from x=0 to 0.4, with Mn2+ added at y=0.1 for Zn2+=0.3 and at 0.3 for Zn2+=0.4. Both sets were dispersed in water with carboxymethyl-dextran or polyacrylic acid coatings to ensure their colloidal stability, even under high magnetic fields. We highlighted the influence of the size and of the Zn2+/Mn2+ doping on the static and dynamical magnetic properties, also through the 1H-NMR-dispersion profile analysis over a wide frequency range and the application of the superparamagnetic relaxation heuristic model. Larger particles exhibited higher nuclear relaxometric efficiency and anisotropy compared to the smaller ones, consistently outperforming the commercial contrast agents. On the other hand, the magnetic response and the nuclear relaxivities are enhanced by a Zn2+ content of x=0.1 ions for approximately 4 nm MNPs and of x=0.4 for approximately 15 nm MNPs, while a slight enhancing effect was obtained by Mn2+ introduction. It is thus shown how a proper size and doping combination provide an attractive way to modify the static and dynamical magnetic properties of MNPs by acting on different spin-spin correlation times dominating in specific frequency intervals, thus enabling the fine-tuning of image contrast properties suitable for magnetic resonance imaging.