Synthesis and in Vitro Evaluation of Magnesium Ferrite Nanoparticles for Application to Magnetic Hyperthermia

Abstract

Recently, the application of magnetic nanoparticles to biomedical field such as a carrier of drug delivery system, a contrast agent of magnetic resonance imaging (MRI), and a heat source of magnetic hyperthermia, is being intensively investigated. In magnetic hyperthermia, magnesium ferrite (MgFe2O4) nanoparticles have been receiving attention as a new heat source because of their frequency-dependence of heating efficiency. Around 300 kHz, which corresponds to the frequency generally used for magnetic hyperthermia, the temperature rise of MgFe2O4 powder was reported to be highest among other kinds of ferrite powder [1]. Furthermore, MgFe2O4 nanoparticles are composed of non-toxic elements, suggesting that they have high biocompatibility. However, a limited number of studies of the influence of MgFe2O4 nanoparticles on cells have been reported; especially the cell mortality associated with cellular uptake of MgFe2O4 nanoparticles is yet to be clearly discussed. In this study, synthesis of MgFe2O4 nanoparticles and the effect of their cellular uptake on the death in human breast cancer cells were investigated. MgFe2O4 nanoparticles were synthesized with two steps. First, an aqueous solution containing magnesium chloride (MgCl2∙6H2O) and iron chloride (FeCl3∙6H2O) at a molar ratio of 1:2 was added slowly into an aqueous sodium hydroxide (NaOH) solution (pH 12.4) at room temperature, followed by stirring for 4 h. Then, the resultant brown powder was annealed at 800°C for 10 min in air with the rate of temperature rise/drop of ~260/~140 °C∙min-1. The nanoparticles were added the medium containing human breast cancer MCF-7 cells, followed by evaluation of cellular uptake and cell mortality with/without exposure to alternating magnetic field (~500 Oe, 325 kHz) for 20 min. MgFe2O4 nanoparticles with a diameter of ~40 nm were obtained after the controlled annealing although the presence of tiny amount of MgO was suggested. The magnetization value at 10000 Oe field and the coercivity of the product was found to be 25 emu∙g-1 and ~60 Oe, respectively, suggesting the ferromagnetic behavior of MgFe2O­4 nanoparticles. When the MgFe2O4 nanoparticles were added to 5 × 105 MCF-7 cells, the amount of internalized particles per cell was increased with an increase in the dose and reached to ~3 ng∙cell-1 at the dose of 5 mg. The percentage of non-viable MCF-7 cells without alternating magnetic field was kept constant below 10% at the dose range from 0 to 5 mg. It should be noted here that ~90% of MCF-7 cells internalized MgFe2O4 nanoparticles at the dose of 5 mg, and the temperature rise and ~90% of cell mortality was observed when subjected to alternating magnetic field. Therefore, it was concluded that heat generated from MgFe2O4 nanoparticles under alternating magnetic field was enough for cancer cell death. Details including the magnetic property of MgFe2O4 nanoparticles annealed with a different rate of heating/cooling will be discussed at the Meeting. [1] K. Konishi et al., J. Magn. Magn. Mater., 272 (2004) 2428.