The Metal Ion Release of Manganese Ferrite Nanoparticles: Kinetics, Effects on Magnetic Resonance Relaxivities, and Toxicity

Mn²⁺ release is particularly important for biological application of manganese-based nanomaterials. However, the Mn²⁺ release profiles of the manganese ferrite nanoparticles are under clarification. Here, we synthesized 3, 10, and 18 nm manganese ferrite nanoparticles (MFNPs) as model systems to study the Mn²⁺ release behavior, size, and pH-dependent kinetics. The Mn²⁺ release kinetic study showed that the first-order kinetic model was suitable for 3 and 10 nm MFNPs, while the Higuchi model was suitable for 18 nm MFNPs in a neutral PBS buffer (pH 7.4). In an acidic PBS buffer (pH 4.8), the Mn²⁺ release from all sizes of MFNPs follows first-order kinetics, which is possible due to the reaction between MFNPs and H⁺. The influence of Mn²⁺ release was evaluated by comparing the variations of magnetic resonance (MR) relaxation and magnetic properties before and after Mn²⁺ release of MFNPs. The results showed that the saturation magnetization (M_s), longitudinal relaxivity (r₁), and transverse relaxivity (r₂) values declined due to Mn²⁺ release, while the ratio of r₂/r₁ increased slightly, showing that all sizes of MFNPs exhibited the same MR mode as the synthesized MFNPs. More importantly, the release kinetics were employed to estimate the toxicity of the released Mn²⁺ in vivo. The potential toxicity is acceptable for MFNP administration since the calculated amount of Mn²⁺ is in the range of safe doses.