Temporal-Compositional Engineering of Manganese Ferrite Nanoparticles for Tunable Theranostic Performance

Mn_xFe_3-xO₄ nanoparticles are versatile spinel ferrites in which controlled Mn substitution tunes cation distribution, magnetic properties, and lattice structure, making them promising for theranostic applications. Mn-induced redistribution of cations between tetrahedral (A) and octahedral (B) sites leads to lattice distortion and modified magnetic interactions, influencing the overall functional behavior of the nanoparticles. The originality of this work lies in demonstrating how compositional and temporal tuning of Mn_xFe_3-xO₄ (x = 0.72-1.68) nanoparticles modulates cation distribution and defect states, thereby influencing biological and theranostic response using a hydrothermal method. Increasing Mn content induces a morphological transition from faceted octahedral particles to nearly spherical structures due to strain relaxation and surface energy redistribution within the distorted spinel lattice. Magnetic measurements and MRI relaxometry reveal a nonlinear dependence of saturation magnetization and relaxivity on Mn concentration, reflecting site-specific Mn²⁺ substitution and localized structural disorder. Of the examined compositions, Mn_0.96Fe_2.40 O₄ demonstrates the highest transverse relaxivity (r₂ = 10.55 mM^-1 s^-1), whereas Mn_1.32Fe_1.68O₄ exhibits the greatest longitudinal relaxivity (r₁ = 0.05 mM^-1 s^-1) standardized to the total concentration of metal ions (Mn + Fe). Moreover, defects induced by Mn incorporation increase ROS generation and apoptosis-related signaling, as evidenced by elevated BAX gene expression, thus strengthening their potential as multifunctional MRI-guided anticancer treatments.