Unraveling the Mn2+ substitution effect on the anisotropy control and magnetic hyperthermia of MnxFe3- xO4 nanoparticles

Abstract

Composition is a key parameter to effectively tune the magnetic anisotropy of magnetic nanoparticles, which in turn can modulate their structural-magnetic properties and final applications. The Mn²⁺ content of manganese ferrite nanoparticles (Mn_xFe_3-xO₄) deeply impacts their structure, anisotropy, magnetism, and their heating capacity. However, a direct correlation between Mn²⁺ content, magnetic properties and heating efficiency is not yet clear. Herein, we report the synthesis of a wide range of Mn_xFe_3-xO₄ with x = 0.14 to 1.40, with similar polyhedral morphologies and sizes (13 to 15 nm). By varying the Mn²⁺ content (in the range of x = 0.0 up to 0.70), we successfully tuned the effective anisotropy while maintaining saturation magnetization nearly constant. Highest Mn²⁺ levels (x = 1.40) lead to structural changes and strain defects reflected in their poor saturation magnetization. Mn²⁺ substitution is not uniform, instead promotes a compositional gradient across the MNPs, with the surface layers having a higher concentration of Mn²⁺ than the core. The Mn²⁺-rich surface likely exhibits superparamagnetic (SPM) relaxation, while the core remains predominantly ferrimagnetic (FiM). Water transference results in cation leaching, promoting vacancies and changes in the local ferrite structure but with a minor impact on the magnetic properties compared with initial MNPs. We obtained the optimal Mn²⁺ content that maximizes anisotropy toward improved specific loss power (SLP) values. The Néel relaxation mechanism is warranted regarding variable composition when sizes and shapes are maintained. Our detailed analysis provides a better understanding of the effect of Mn²⁺ substitution on the heating efficiency through anisotropy modulation and straightforward guidance on optimizing MNP design for magnetic hyperthermia.

Fig. 1. (A) TEM images of Mn_xFe_3−xO₄ MNPs with varying Mn²⁺ content (x_Empiric = 0.14 to 1.40). The samples with the initial Fe/Mn precursor amount of x_Theo = 0.40, 0.75, 1.0, and 1.50 are highlighted with blue, green, red, and brown boxes, respectively. Inset: Empirical x value for each sample determined by ICP-OES along with their respective size diameters. Scale bar: 50 nm. (B) STEM-EDX mapping images of Mn_xFe_3−xO₄ MNPs with the lowest, medium, and highest content of Mn²⁺ (x_Empiric = 0.14, 0.70, 1.40). Scale bar: 50 nm (x_Empiric = 0.14 and 0.70), 20 nm (x_Empiric = 1.40).

Fig. 2. (A) Evolution of the XRD pattern of the full set of Mn_xFe_3−xO₄ MNPs with x = 0.14 up to 1.40 with the corresponding Bragg positions of MnFe₂O₄ reference (black lines) and Fe_1−xO (red asterisk). (B) HRTEM images of samples with x_Empiric = 0.23 and 0.37 and their FFT and inverse FFT of the plane (220). (C) Energy splitting of the Mn 3s and Fe 3s doublets as a function of the ferrite stoichiometry computed from XPS. (D) Mn/Fe atomic ratios computed from the 2p and 3s XPS signals vs. the compositional data obtained from ICP, for the samples with ferrite stoichiometries of x_Empiric = 0.23, 0.37, 0.47 and 1.40. (E) Mössbauer spectra of x_Empiric = 0.14, 0.23 and 0.37 MNPs.

Fig. 3. (A) Static magnetization cycles recorded at 300 K for the MNPs and (B) low field region of the magnetization cycles.

Fig. 4. Influence of the PMAO coating on the structural and magnetic properties of Mn_xFe_3−xO₄ MNPs. (A) TEM images of selected Mn_x@PMAO samples and their corresponding histogram size distribution. Theoretical and empirical x values obtained in organic and aqueous media are shown. (B) FT-IR spectra of Mn_x@PMAO with x_Empiric = 0.07 and 1.10, respectively. (C) Comparison between XRD patterns with initial composition (organic) of x_Empiric = 0.14, and 1.40, and after water transference x_Empiric = 0.07, and 1.10, respectively. (D) Magnetization cycles of Mn_x@PMAO series (x_Empiric = 0.07 up to 1.10) compared with Fe₃O₄ (x = 0.0) obtained using the same synthetic procedure at 300 K.

Fig. 5. Effect of the Mn²⁺ content on the heating efficiency of Mn_xFe_3−xO₄ MNPs. SLP values obtained by the calorimetric method for Mn_xFe_3−xO₄ MNPs with fixed frequencies of (A) f = 155 kHz and (B) f = 763 kHz under field intensity (H) ranging from 3.8 up to 44.6 kA m⁻¹. (C) Dynamic magnetization curves obtained at 150 kHz and 24 kA m⁻¹ for samples with x_Empiric = 0.0, 0.07, 0.30, 0.40, 0.60, and 1.10. Inset: Magnification of the low field region. (D) SAR values of the corresponding samples (with x_Empiric = 0.0 up to 1.10). (E) Dynamic magnetization curves obtained at 300 kHz and 24 kA m⁻¹ of samples with x_Empiric = 0.07 and 0.70, respectively, compared to samples without Mn²⁺ (x = 0.0). Inset: Low field region. (F) SAR value of samples measured in (E). Black dots represent the Hf values for each condition tested. Safe clinic Hf values are delimited with a red dotted line.

Fig. 6. (A) and (B) Viability assay of the MIA PaCa-2 cell line loaded Mn_xFe_3−xO₄ MNPs, with x = 0.07 and 0.60, respectively. (C) Fluorescence images taken after 24 h of incubation with 100 μg mL⁻¹ of TAMRA-labelled MNPs in MIA PaCa-2 cells. Nuclei (blue), F-actin (green) and MNPs (red). Scale bar = 20 μm.

Susel Del Sol-Fernández