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Abstract
We report the synthesis of magnetite nanoparticles (IOMNPs) using the polyol method performed at elevated temperature (300 °C) and high pressure. The ferromagnetic polyhedral IOMNPs exhibited high saturation magnetizations at room temperature (83 emu/g) and a maximum specific absorption rate (SAR) of 2400 W/gFe in water. The uniform dispersion of IOMNPs in solid matrix led to a monotonous increase of SAR maximum (3600 W/gFe) as the concentration decreased. Cytotoxicity studies on two cell lines (cancer and normal) using Alamar Blues and Neutral Red assays revealed insignificant toxicity of the IOMNPs on the cells up to a concentration of 1000 μg/mL. The cells internalized the IOMNPs inside lysosomes in a dose-dependent manner, with higher amounts of IOMNPs in cancer cells. Intracellular hyperthermia experiments revealed a significant increase in the macroscopic temperatures of the IOMNPs loaded cell suspensions, which depend on the amount of internalized IOMNPs and the alternating magnetic field amplitude. The cancer cells were found to be more sensitive to the intracellular hyperthermia compared to the normal ones. For both cell lines, cells heated at the same macroscopic temperature presented lower viability at higher amplitudes of the alternating magnetic field, indicating the occurrence of mechanical or nanoscale heating effects.
Highlights
Since the validation of ferrimagnetic iron oxide magnetic nanoparticles, IOMNPs, by the U.S Food and Drug Administration [1], this class of magnetic nanoparticles has been the subject of intense research for their potentiality in a widespread number of biomedical and pharmaceutical applications [2,3,4,5,6]
The polyol route becomes a versatile way for the synthesis of magnetic nanoparticles (MagNPs) with variable sizes, shapes, and compositions that can be tuned by the nature of the magnetic precursors and precipitator, the choice of the solvents, the presence of extra stabilizer, and the temperature and duration of the reaction [21,22,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]
Cytotoxicity studies on two cell lines (A549 cancer cell line and human gingival fibroblasts (HGF) normal cell line) using Alamar Blue (AB) and Neutral Red (NR) assays revealed that the cells internalized the IOMNPs in a dose-dependent manner, with higher amounts of IOMNPs in A549 cells
Summary
Since the validation of ferrimagnetic iron oxide magnetic nanoparticles, IOMNPs (magnetite—Fe3O4 or maghemite—Fe2O3), by the U.S Food and Drug Administration [1], this class of magnetic nanoparticles has been the subject of intense research for their potentiality in a widespread number of biomedical and pharmaceutical applications [2,3,4,5,6]. The clinical applications of MH based tumor treatments for glioblastoma and prostate cancer were used in conjunction with chemotherapy and radiotherapy [10] To overcome these limitations, intense research efforts have been devoted to the fabrication of IOMNPs with significantly enhanced heating capabilities by controlling their composition, size, size distribution, shape, and surface coatings [11]. Intense research efforts have been devoted to the fabrication of IOMNPs with significantly enhanced heating capabilities by controlling their composition, size, size distribution, shape, and surface coatings [11] Notwithstanding these efforts, the maximum heating ability of IOMNPs in an alternating magnetic field (AMF) is limited both by their intrinsic physical properties and by the safety limits imposed for the magnetic field parameters (H amplitude of the AMF and f frequency) such as H × f < 5 × 109 Am−1s−1 [12]. These effects leading to cellular death need further, more detailed investigations aiming at explaining the actual mechanisms relating the IOMNPs-MH characteristics to the biological effects
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