Abstract
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) Fe3O4-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/gMNP for the small monocrystalline MNPs and only 400 W/gMNP 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.
Highlights
Magnetic nanoparticles (MNPs) represent one of the main classes of nanoparticles (NPs) which are currently in the research spotlight, with many potential applications in the field of the life sciences: magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, drug delivery, hyperthermia, and cell separation [1]
This new therapeutic concept, called magnetic hyperthermia (MH) [5], relies on the heat released by the magnetic nanoparticles (MNPs) exposed to an externally applied alternating magnetic field (AMF) which is used to increase the temperature of the cancer cells, up to a level at which apoptosis can be initiated
Two classes of Fe3 O4 MNPs were synthesized by using a polyol based method and systematically investigated and compared for their structural, magnetic, hyperthermic, cytotoxic and cell uptake properties
Summary
Magnetic nanoparticles (MNPs) represent one of the main classes of nanoparticles (NPs) which are currently in the research spotlight, with many potential applications in the field of the life sciences: magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, drug delivery, hyperthermia, and cell separation [1]. Besides the inconvenient that MNPs are not water-dispersible, this method can lead to MNPs formed by mixed Fe3 O4 magnetite and FeO wüstite phases with low saturation magnetization and SAR values They require a post-synthesis treatment in order to improve their magnetic properties and for rendering them both hydrophilic and biocompatible [19]. In order to address these challenges, complete toxicology studies are mandatory in order to understand the impact of the exposure of cell cultures to MNPs [24] Based on these experimental observations, in the present study we propose to systematically investigate and compare the structural, magnetic, hyperthermic, cytotoxicity and cell uptake properties of two classes of MNPs: Fe3 O4 MNPs synthesized in PEG 200 and ethylene glycol (EG), called in the followings small and large Fe3 O4 MNPs, respectively. The MNPs cytotoxicity has been assessed by using the standard 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay up to a concentration of 0.2 mg/mL, while their uptake by the cells was monitored by Transmission Electron Microscopy (TEM)
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