Iron oxide-manganese oxide nanoparticles with tunable morphology and switchable MRI contrast mode triggered by intracellular conditions

Abstract

Stimuli-responsive nanomaterials are very attractive for biomedical applications. They can be activated through external stimuli or by the physico-chemical conditions present in cells or tissues. Here, we describe the preparation of hybrid iron oxide-manganese oxide core-satellite shell nanostructures that change their contrast mode in magnetic resonance imaging (MRI) from T₂ to T₁, after being internalized by cells. This occurs by the dissolution of the MnO₂ of the shell, preserving intact the iron oxide at the core. First, we study the seeded-growth synthesis of iron oxide-manganese oxide nanoparticles studying the effect of varying the core size of the magnetic seeds and the concentration of the surfactant. This allows tuning the size and shape of the final hybrid nanostructure. Then, we show that the shell can be removed by a redox reaction with glutathione, which is naturally present inside the cells at much higher concentrations than outside the cells. Finally, the dissolution of the MnO₂ shell and the change in the contrast mode is confirmed in cell cultures. After this process, the iron oxide nanoparticles at the core remain intact and are still active as heating mediators when an alternating magnetic field is applied.

Keywords: Hybrid nanoparticles; Intracellular-responsive; MRI; Magnetic hyperthermia; Stimuli-responsive.