Ultrasmall Manganese Oxide Nanoparticles as Contrast Agents for T₁-T₂ Dual-Modal Magnetic Resonance Imaging

Recently, Manganese oxide (MnO) nanoparticles have garnered considerable research interest due to their high applicability in Magnetic Resonance Imaging (MRI), leveraging their light-enhancing properties. In present work, ultrasmall and monodisperse MnO nanoparticles were synthesized via thermal decomposition and subsequently coated with poly-(maleic anhydride-<i>alt</i>-1-octadecene) (PMAO) to stabilize the colloidal dispersion and optimize image contrast. The impact of the surfactants (oleic acid (OA) and oleylamine (OLA) surfactants with ratio 1:1) and the reaction temperature on nanoparticle characteristics was systematically studied. Optimal synthesis conditions, including a surfactant concentration of 600 mM for both OA and OLA and a reaction temperature of 320 °C, yielded monodisperse, spherical MnO nanoparticles with a uniform average particle size of 5.0 ± 0.5 nm. The MRI contrast properties of the manganese oxide nanoparticles, including longitudinal (<i>r</i> ₁) and transverse (<i>r</i> ₂) relaxation rates, were measured at a magnetic field strength of 1.5 T. The nanoparticle-containing liquid exhibited significant positive contrast enhancement in T₁-weighted images, attributed to the high longitudinal relaxivity (<i>r</i> ₁) and low <i>r</i> ₂/<i>r</i> ₁ ratio of the nanoparticles (<i>r</i> ₁ = 5.99, <i>r</i> ₂ = 21.7 mM^-1 s^-1, <i>r</i> ₂/<i>r</i> ₁ = 3.62 at 1.5 T). In vitro, cytotoxicity studies on normal HEK293 cells revealed no adverse effects associated with the nanoparticles. In vivo experiments on mouse showed that images of body parts were observed after injection of MnO@PMAO NPs with both T₁-T₂ imaging modes, especially T₁ imaging. These findings collectively support the potential of MnO@PMAO nanoparticles as a promising positive contrast agent for MRI applications.