Enhanced reduction in cell viability by hyperthermia induced by magnetic nanoparticles (original) (raw)
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2017
In this paper, we simulate magnetic hyperthermia process on a mathematical phantom model representing cancer tumor and its surrounding healthy tissues. The temperature distribution throughout the phantom model is obtained by solving the bio-heat equations and the consequent cell death amount is calculated using correlations between the tissue local temperature and the cell death rate. To have an estimate of heat generated from typical magnetic nanoparticles, magnetite nanoparticles are synthesized and the heat dissipation amount from the synthesized nanoparticles exposed to an alternating magnetic field is measured and used in the computer simulation. The impact of the amount of heat generated from the magnetic nanoparticles exposed to an alternating magnetic field, their distribution patterns in the tumor and hyperthermia process duration time on the cell death rate in both cancer and healthy tissues are investigated. It is indicated that while various factors contributing in the h...
Magnetic nanoparticle-based hyperthermia for cancer treatment
Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznań and Polish Society of Radiation Oncology, 2013
Nanotechnology involves the study of nature at a very small scale, searching new properties and applications. The development of this area of knowledge affects greatly both biotechnology and medicine disciplines. The use of materials at the nanoscale, in particular magnetic nanoparticles, is currently a prominent topic in healthcare and life science. Due to their size-tunable physical and chemical properties, magnetic nanoparticles have demonstrated a wide range of applications ranging from medical diagnosis to treatment. Combining a high saturation magnetization with a properly functionalized surface, magnetic nanoparticles are provided with enhanced functionality that allows them to selectively attach to target cells or tissues and play their therapeutic role in them. In particular, iron oxide nanoparticles are being actively investigated to achieve highly efficient carcinogenic cell destruction through magnetic hyperthermia treatments. Hyperthermia in different approaches has bee...
Pharmaceutics
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 m...
Journal of Physics D: Applied Physics, 2008
Magnetic nanoparticles are being developed for a wide range of biomedical applications. In particular, hyperthermia involves heating the magnetic nanoparticles through exposure to an alternating magnetic field. These materials offer the potential to selectively treat cancer by heating cancer tissue locally and at the cellular level. This may be a successful method if there are enough particles in a tumor possessing a sufficiently high specific absorption rate (SAR) to deposit heat quickly while minimizing thermal damage to surrounding tissue. High SAR magnetic nanoparticles have been developed and used in mouse models of cancer. The magnetic nanoparticles comprise iron oxide magnetic cores (mean core diameter of 50 nm) surrounded by a dextran layer shell for colloidal stability. In comparing two similar systems, the saturation magnetization is found to play a crucial role in determining the SAR, but is not the only factor of importance. (A difference in saturation magnetization of a factor of 1.5 yields a difference in SAR of a factor of 2.5 at 1080 Oe and 150 kHz.) Variations in the interactions due to differences in the dextran layer, as determined through neutron scattering, also play a role in the SAR. Once these nanoparticles are introduced into the tumor, their efficacy, with respect to tumor growth, is determined by the location of the nanoparticles within or near the tumor cells and the association of the nanoparticles with the delivered alternating magnetic field (AMF). This association (nanoparticle SAR and AMF) determines the amount of heat generated. In our setting, the heat generated and the time of heating (thermal dose) provides a tumor gross treatment response which correlates closely with that of conventional (non-nanoparticle) hyperthermia. This being said, it appears specific aspects of the nanoparticle hyperthermia cytopathology mechanism may be very different from that observed in conventional cancer treatment hyperthermia.
In vitro hyperthermic effect of magnetic fluid on cervical and breast cancer cells
Scientific Reports, 2020
Self-regulating temperature-controlled nanoparticles such as Mn–Zn ferrite nanoparticles based magnetic fluid can be a better choice for magnetic fluid hyperthermia because of its controlled regulation of hyperthermia temperature window of 43–45 °C. To test this hypothesis magnetic fluid with said properties was synthesized, and its effect on cervical and breast cancer cell death was studied. We found that the hyperthermia window of 43–45 °C was maintained for one hour at the smallest possible concentration of 0.35 mg/mL without altering the magnetic field applicator parameters. Their hyperthermic effect on HeLa and MCF7 was investigated at the magnetic field of 15.3 kA/m and frequency 330 kHz, which is close to the upper safety limit of 5 * 109 A/m s. We have tested the cytotoxicity of synthesized Mn–Zn ferrite fluid using MTT assay and the results were validated by trypan blue dye exclusion assay that provides the naked eye microscopic view of actual cell death. Since cancer cells...
Nanomaterials, 2021
Magnetic iron oxide nanoparticles are the most desired nanomaterials for biomedical applications due to their unique physiochemical properties. A facile single-step process for the preparation of a highly stable and biocompatible magnetic colloidal suspension based on citric-acid-coated magnetic iron oxide nanoparticles used as an effective heating source for the hyperthermia treatment of cancer cells is presented. The physicochemical analysis revealed that the magnetic colloidal suspension had a z-average diameter of 72.7 nm at 25 °C with a polydispersity index of 0.179 and a zeta potential of −45.0 mV, superparamagnetic features, and a heating capacity that was quantified by an intrinsic loss power analysis. Raman spectroscopy showed the presence of magnetite and confirmed the presence of citric acid on the surfaces of the magnetic iron oxide nanoparticles. The biological results showed that breast adenocarcinoma cells (MDA-MB-231) were significantly affected after exposure to the...
Pharmaceutics
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 sensitiv...
Purpose To investigate the effects of alternating magnetic fields (AMF) on the death rate of dendritic cells (DCs) loaded with magnetic nanoparticles (MNPs) as heating agents. AMF exposure time and amplitude as well as the MNPs concentration were screened to assess the best conditions for a controlled field-induced cell death. Methods Human-monocyte-derived DCs were co-incubated with dextran-coated MNPs. The cells were exposed to AMF (f0260 kHz; 0<H 0 <12.7 kA/m) for intervals from 5 to 15 min. Morphology changes were assessed by scanning electron microscopy. Cell viability was measured by Trypan blue and fluorescence-activated cell sorting (FACS) using Annexin-propidium iodide markers. Results We were able to control the DCs viability by a proper choice AMF amplitude and exposure time, depending on the amount of MNPs uploaded. About 20% of cells showed Annexinnegative/PI-positive staining after 5-10 min of AMF exposure. Conclusions Controlled cell death of MNP-loaded DCs can be obtained by adequate tuning of the physical AMF parameters and MNPs concentration. Necrotic-like populations were observed after exposure times as short as 10 min, suggesting a fast underlying mechanism for cell death. Power absorption by the MNPs might locally disrupt endosomic membranes, thus provoking irreversible cell damage.
Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties
Molecules, 2016
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.
Pharmaceutical Research, 2014
Purpose Tumor cells can be effectively inactivated by heating mediated by magnetic nanoparticles. However, optimized nanomaterials to supply thermal stress inside the tumor remain to be identified. The present study investigates the therapeutic effects of magnetic hyperthermia induced by superparamagnetic iron oxide nanoparticles on breast (MDA-MB-231) and pancreatic cancer (BxPC-3) xenografts in mice in vivo. Methods Superparamagnetic iron oxide nanoparticles, synthesized either via an aqueous (MF66; average core size 12 nm) or an organic route (OD15; average core size 15 nm) are analyzed in terms of their specific absorption rate (SAR), cell uptake and their effectivity in in vivo hyperthermia treatment. Results Exceptionally high SAR values ranging from 658± 53 W*g Fe −1 for OD15 up to 900±22 W*g Fe −1 for MF66 were determined in an alternating magnetic field (AMF, H=15.4 kA*m −1 (19 mT), f=435 kHz). Conversion of SAR values into systemindependent intrinsic loss power (ILP, 6.4±0.5 nH*m 2 *kg −1 (OD15) and 8.7±0.2 nH*m 2 *kg −1 (MF66)) confirmed the markedly high heating potential compared to recently published data. Magnetic hyperthermia after intratumoral nanoparticle injection results in dramatically reduced tumor volume in both cancer models, although the applied temperature dosages measured as CEM43T90 (cumulative equivalent minutes at 43°C) are only between 1 and 24 min. Histological analysis of magnetic hyperthermia treated tumor tissue exhibit alterations in cell viability (apoptosis and necrosis) and show a decreased cell proliferation. Conclusions Concluding, the studied magnetic nanoparticles lead to extensive cell death in human tumor xenografts and are considered suitable platforms for future hyperthermic studies. KEY WORDS CEM43T90 . in vivo . iron oxide nanoparticles . magnetic hyperthermia . temperature dose ABBREVIATIONS AMF Alternating magnetic field CEM43 Cumulative equivalent minutes at 43°C CEM43T90 Cumulative equivalent minutes at a T90 temperature of 43°C ILP Intrinsic loss power MNP Magnetic nanoparticles SAR Specific absorption rate T90 Temperature exceeded by 90% of the tumor surface