Manganese and zinc ferrite magnetic nanoparticles (MNPs) were successfully synthesized using the polyol method in ethylene glycol and were found to have high saturation magnetization values (90–95 emu/g at 4 K) when formed by ~30-nm crystallites assembled in an ~80-nm multicore structure. Hyperthermia data revealed a sigmoidal dependence of the specific absorption rate (SAR) on the alternating magnetic field (AMF) amplitude, with remarkable saturation SAR values in water of ~1200 W/gFe+Mn and ~800 W/gFe+Zn for the Mn and Zn ferrites, respectively. The immobilization of the MNPs in a solid matrix reduced the maximum SAR values by ~300 W/gFe+Mn, Zn for both ferrites. The alignment of the MNPs in a uniform static magnetic field, before their immobilization in a solid matrix, significantly increased their heating performance. Toxicity assays performed in four cell lines revealed a lower toxicity for the Mn ferrites, while in the case of the Zn ferrites, only ~50% of cells were viable upon their incubation for 24 h with 0.2 mg/mL of MNPs. Cellular uptake experiments revealed that both MNPs entered the cells in a time-dependent manner, as they were found initially in endosomes and later in the cytosol. All of the studied cell lines were more sensitive to the ZnFe2O4 MNPs.

Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe 3 O 4 -MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol (EG), respectively. They were systematically investigated by means of X-ray diffraction, transmission electron microscopy and vibration sample magnetometry. Hyperthermia measurements showed that Specific Absorption Rate (SAR) dependence on the external alternating magnetic field amplitude (up to 65 kA/m, 355 kHz) presented a sigmoidal shape, with remarkable SAR saturation values of~1400 W/g MNP for the small monocrystalline MNPs and only 400 W/g MNP for the large polycrystalline MNPs, in water. SAR values were slightly reduced in cell culture media, but decreased one order of magnitude in highly viscous PEG1000. Toxicity assays performed on four cell lines revealed almost no toxicity for the small MNPs and a very small level of toxicity for the large MNPs, up to a concentration of 0.2 mg/mL. Cellular uptake experiments revealed that both MNPs penetrated the cells through endocytosis, in a time dependent manner and escaped the endosomes with a faster kinetics for large MNPs. Biodegradation of large MNPs inside cells involved an all-or-nothing mechanism.

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.

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Spinel ferrite nanoparticles represent a class of magnetic nanoparticles (MNPs) with enormous potential in magnetic hyperthermia. In this study, we investigated the magnetic and heating properties of spinel soft NiFe2O4, MnFe2O4, and hard CoFe2O4 MNPs of comparable sizes (12–14 nm) synthesized by the polyol method. Similar to the hard ferrite, which predominantly is ferromagnetic at room temperature, the soft ferrite MNPs display a non-negligible coercivity (9–11 kA/m) arising from the strong interparticle interactions. The heating capabilities of ferrite MNPs were evaluated in aqueous media at concentrations between 4 and 1 mg/mL under alternating magnetic fields (AMF) amplitude from 5 to 65 kA/m at a constant frequency of 355 kHz. The hyperthermia data revealed that the SAR values deviate from the quadratic dependence on the AMF amplitude in all three cases in disagreement with the Linear Response Theory. Instead, the SAR values display a sigmoidal dependence on the AMF amplitude, with a maximum heating performance measured for the cobalt ferrites (1780 W/gFe+Co), followed by the manganese ferrites (835 W/gFe+Mn), while the nickel ferrites (540 W/gFe+Ni) present the lowest values of SAR. The heating performances of the ferrites are in agreement with their values of coercivity and saturation magnetization.

Increasing the biocompatibility, cellular uptake, and magnetic heating performance of ferromagnetic iron-oxide magnetic nanoparticles (F-MNPs) is clearly required to efficiently induce apoptosis of cancer cells by magnetic hyperthermia (MH). Thus, F-MNPs were coated with silica layers of different thicknesses via a reverse microemulsion method, and their morphological, structural, and magnetic properties were evaluated by multiple techniques. The presence of a SiO2 layer significantly increased the colloidal stability of F-MNPs, which also enhanced their heating performance in water with almost 1000 W/gFe as compared to bare F-MNPs. The silica-coated F-MNPs exhibited biocompatibility of up to 250 μg/cm2 as assessed by Alamar Blues and Neutral Red assays on two cancer cell lines and one normal cell line. The cancer cells were found to internalize a higher quantity of silica-coated F-MNPs, in large endosomes, dispersed in the cytoplasm or inside lysosomes, and hence were more sensitive to in vitro MH treatment compared to the normal ones. Cellular death of more than 50% of the malignant cells was reached starting at a dose of 31.25 μg/cm2 and an amplitude of alternating magnetic field of 30 kA/m at 355 kHz.

The applications of ferrimagnetic nanoparticles (F-MNPs) in magnetic hyperthermia (MH) are restricted by their stabilization in microscale aggregates due to magnetostatic interactions significantly reducing their heating performances. Coating the F-MNPs in a silica layer is expected to significantly reduce the magnetostatic interactions, thereby increasing their heating ability. A new fast, facile, and eco-friendly oil-in-water microemulsion-based method was used for coating Zn0.4Fe2.6O4 F-MNPs in a silica layer within 30 min by using ultrasounds. The silica-coated clusters were characterized by various physicochemical techniques and MH, while cytotoxicity studies, cellular uptake determination, and in vitro MH experiments were performed on normal and malignant cell lines. The average hydrodynamic diameter of silica-coated clusters was approximately 145 nm, displaying a high heating performance (up to 2600 W/gFe). Biocompatibility up to 250 μg/cm2 (0.8 mg/mL) was recorded by Alamar Blue and Neutral Red assays. The silica-coating increases the cellular uptake of Zn0.4Fe2.6O4 clusters up to three times and significantly improves their intracellular MH performances. A 90% drop in cellular viability was recorded after 30 min of MH treatment (20 kA/m, 355 kHz) for a dosage level of 62.5 μg/cm2 (0.2 mg/mL), while normal cells were more resilient to MH treatment.

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