D-Alpha-Tocopheryl Poly(ethylene Glycol 1000) Succinate-Coated Manganese-Zinc Ferrite Nanomaterials for a Dual-Mode Magnetic Resonance Imaging Contrast Agent and Hyperthermia Treatments

Abstract

Manganese-zinc ferrite (MZF) is known as high-performance magnetic material and has been used in many fields and development. In the biomedical applications, the biocompatible MZF formulation attracted much attention. In this study, water-soluble amphiphilic vitamin E (TPGS, d-alpha-tocopheryl poly(ethylene glycol 1000) succinate) formulated MZF nanoparticles were synthesized to serve as both a magnetic resonance imaging (MRI) contrast agent and a vehicle for creating magnetically induced hyperthermia against cancer. The MZF nanoparticles were synthesized from a metallic acetylacetonate in an organic phase and further modified with TPGS using an emulsion and solvent-evaporation method. The resulting TPGS-modified MZF nanoparticles exhibited a dual-contrast ability, with a longitudinal relaxivity (35.22 s^-1 mM Fe^-1) and transverse relaxivity (237.94 s^-1 mM Fe^-1) that were both higher than Resovist^®. Furthermore, the TPGS-assisted MZF formulation can be used for hyperthermia treatment to successfully suppress cell viability and tumor growth after applying an alternating current (AC) electromagnetic field at lower amplitude. Thus, the TPGS-assisted MZF theranostics can not only be applied as a potential contrast agent for MRI but also has potential for use in hyperthermia treatments.

Keywords: hyperthermia; in vivo; magnetic resonance imaging; manganese-zinc ferrite; theranostic.

Figure 1

Characterization of the as-synthesized MZF. The TEM images of (A) Mn₀.₂Zn₀.₈Fe₂O₄, (B) Mn₀.₅Zn₀.₅Fe₂O₄, and (C) Mn₀.₈Zn₀.₂Fe₂O₄. (D) The hysteresis loops of different Mn/Zn ratio MZF nanoparticles (black: Mn₀.₂Zn₀.₈Fe₂O₄, red: Mn₀.₅Zn₀.₅Fe₂O₄, blue: Mn₀.₈Zn₀.₂Fe₂O₄, green: Mn₀.₅Zn₀.₅Fe₂O₄@TPGS) and TPGS formulated Mn₀.₅Zn₀.₅Fe₂O₄ nanoparticles formulations (MZF@TPGS). (E) The XRD pattern of as synthesized Mn₀.₅Zn₀.₅Fe₂O₄ nanoparticles.

Figure 2

(A) The size distribution and (B) a TEM image of the MZF@TPGS formulations. (C) Photograph of as-synthesized MZF dispersed in hexane and modified MZF@TPGS in an aqueous.

Figure 3

(A) T₁-weighted and T₂-weighted relaxivity plots measured by a pulsed NMR Minispec. (B) MR images of the MZF@TPGS formulations taken by a 3 T clinical MR scanner.

Figure 4

(A) Viability of KB cells evaluated by the MTT assay after the treatments with the MZF@TPGS formulations and after hyperthermia. The results are presented as the viability means ± standard deviations. (n = 3) (B) The KB cells cellular uptake of the MZF@TPGS formulations in at 37 °C from 1 to 12 h, which was evaluated by Prussian blue staining and visualized by optical microscopy with digital camera.

Figure 5

In vivo studies of KB tumor-bearing mice before and 24 h after administering of MZF@TPGS formulations. (A) T₁-weighted and (B) T₂-weighted animal MR images taken by a 7 T animal MR scanner. (C) Analysis of the photo brightness intensity using ImageJ. (* p < 0.05) (D) The images of H&E staining and Prussian blue staining of liver and tumor sections from the KB tumor-bearing mice 24 h. The arrows indicate iron staining.

Figure 6

In vivo antitumor effects studies of MZF@TPGS formulations in KB tumor-bearing mice. (n = 3 in control, n = 4 in hyperthermia, n = 5 in MZF@TPGS with hyperthermia) (A) Tumor size and (B) body weight of the different groups over the experimental period of 14 days (* p < 0.05).

Figure 7

(A) H&E staining and the (B) Prussian blue staining of tumor, liver and spleen sections from mice after treatment with the MZF@TPGS formulations and hyperthermia.