Magnetic Fluid Hyperthermia Therapy Research Articles

In vitro evaluation of magnetic fluid hyperthermia therapy on breast cancer cells using monodispersed Mn0.5Zn0.5Fe2O4 nanoflowers

Magnetic fluid hyperthermia (MFH) is emerging as an alternate treatment therapy for cancer of different types, due to its potential low side effects and relatively less painless treatment option. However, the implementation of standalone therapy is still challenging and needs research to optimize the effective killing of 100% cancerous tissues, number of therapy sessions, time duration of the therapy, controlled hyperthermia window temperature, etc. We report here the potential of nanoclusters (nanoflowers) based dispersion and on an in vitro study on breast cancer cells (MDA-MB-231). The nanoclusters were characterized using XRD, TEM, DLS, VSM and MFH, before investigating them with breast cancer cells. The effect of MFH, before and after the treatment of induction heating on MDA-MB-231 cells, were also studied. Results show that the MFH is capable of killing almost 87% of cells within 30 min of treatment on cells in the presence of magnetic nanoclusters. This shows the potential of developing nanoflowers for the treatment of cancer over other single domain magnetic nanoparticles.

Dextran-coated Fe3 O4 Nanoparticles for Hyperthermia Therapy Application

In the present work, nanocrystals of magnetite were prepared by alkaline precipitation. The precursor used for synthesis was ferrous chloride only and the reaction was carried out in absence of any oxidant. Dextran is a material with excellent biocompatibility, water solubility and low cytotoxicity. Hence it was chosen as a potential coating material for the magnetic nanoparticles (MNPs). Both bare and coated MNPs (Fe3O4 and D- Fe3O4) showed particle size of diameter 20.8±4.1 nm and 16.3±3.2 nm, respectively. The magnetization values of both the MNPs were 53.62 emu/g and 47.86 emu/g at room temperature, respectively. The negligible coercivity and remanence values at room temperature implied superparamagnetic behaviour of the MNPs. Zeta potential of both bare and coated nanoparticles showed higher colloidal stability of coated nanoparticles than the bare one at a pH range of 2-10. The MNPs are studied for their heating induction abilities at 167.6 Oe, 251.4 Oe and 335.2 Oe (equivalent to 13.3, 20.0 and 26.7 kA m-1, respectively), in order to use them in magnetic fluid hyperthermia therapy. At 335.2 Oe, DFe 3O4 showed maximum Specific Absorption Rate (SAR) of 120.25 W/g, while bare MNPs showed SAR of 79.32 W/g. Both the particles had no cytotoxic effect on L929 cell line showing their strong possibility to be used for in vivo applications. The further work is in the process.

Iron-Based Ceramic Composite Nanomaterials for Magnetic Fluid Hyperthermia and Drug Delivery.

Because of the unique physicochemical properties of magnetic iron-based nanoparticles, such as superparamagnetism, high saturation magnetization, and high effective surface area, they have been applied in biomedical fields such as diagnostic imaging, disease treatment, and biochemical separation. Iron-based nanoparticles have been used in magnetic resonance imaging (MRI) to produce clearer and more detailed images, and they have therapeutic applications in magnetic fluid hyperthermia (MFH). In recent years, researchers have used clay minerals, such as ceramic materials with iron-based nanoparticles, to construct nanocomposite materials with enhanced saturation, magnetization, and thermal effects. Owing to their unique structure and large specific surface area, iron-based nanoparticles can be homogenized by adding different proportions of ceramic minerals before and after modification to enhance saturation magnetization. In this review, we assess the potential to improve the magnetic properties of iron-based nanoparticles and in the preparation of multifunctional composite materials through their combination with ceramic materials. We demonstrate the potential of ferromagnetic enhancement and multifunctional composite materials for MRI diagnosis, drug delivery, MFH therapy, and cellular imaging applications.

On the relaxation time of interacting superparamagnetic nanoparticles and implications for magnetic fluid hyperthermia.

A critical discussion on the presently available models for the relaxation time of magnetic nanoparticles approaching the superparamagnetic regime in the presence of interparticle dipolar interactions is considered. The direct implications of such interactions for magnetic fluid hyperthermia therapy through susceptibility loss mechanisms give rise to an indirect method for their study via specific absorption rate measurements performed on ferrofluids of different volume fractions. The theoretical support for the specific evolution of the relaxation time constant and the anisotropy energy barrier versus the interparticle interactions in a perturbation approach of the simple Néel expression for the relaxation time is provided via static and time-dependent micromagnetic simulations.

Superparamagnetic CoFe2O4@Au with High Specific Absorption Rate and Intrinsic Loss Power for Magnetic Fluid Hyperthermia Applications

CoFe2O4 nanoparticles (NPs) and surface modified with gold (Au) have been synthesized by a thermal decomposition method. The obtained NPs and formation of CoFe2O4@Au core–shell (CS) were confirmed by characterizing their structural and optical properties using X-ray powder diffraction (XRD) patterns, Fourier transform infrared spectroscopy, Raman spectroscopy, UV–Visible and photoluminescence studies. Morphological and compositional studies were carried out using high-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy, while the magnetic properties were determined using alternating gradient magnetometer and Mossbauer to define the magneto-structural effects of shell formation on the core NPs. Induction heating properties of CoFe2O4 and CoFe2O4@Au CS magnetic nanoparticles (MNPs) have been investigated and correlated with magneto-structural properties. Specific absorption rate and intrinsic loss power were calculated for these MNPs within the human tolerable range of frequency and amplitude, suggesting their potential in magnetic fluid hyperthermia therapy for possible cancer treatment.

Heat transfer of PEGylated cobalt ferrite nanofluids for magnetic fluid hyperthermia therapy: In vitro cellular study

Hyperthermia generally means as increasing the temperature of particular region of body to rise 5 °C above the body’s physiological temperature. Here, we investigate the thermal therapy of PEGylated cobalt ferrite nanoparticles prepared by hydrothermal approach on cancerous cell line in the alternative current magnetic field. To characterize of the magnetic nanoparticles (MNPs), scanning electron microscopy, dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, and vibrating sample magnetometer were used. X-ray diffraction analysis confirmed the spinel phase formation of the MNPs. Cytotoxicity of MNPs using MTT assay on L929 cell lines showed the PEGylated MNPs extraordinary biocompatibility. Specific loss power (SLP) were calculated for neat and PEGylated MNPs in aqueous solution in radio frequency region (300–400 kHz). Power absorbed by neat and PEGylated cobalt ferrite were measured as a function of frequency and MNPs concentration. The maximum SLP was 31.8 W/g for coated nanoparticles (MNPs + PEG) in concentration of 0.0025 gr/mL at applied frequency of 350 kHz. Magnetic fluid hyperthermia of MCF7 breast cancer cells were shown up to 90 percent of cell death in 350 kHz. Simulation studies approved the elevated temperature of the PEGylated MNPs to 42 °C in the tumor after 10 min of MNPs intratumorally injection. This study shows increase in rate of heating in the tumor when the temperature of injected MNPs is approximately equal to the body temperature (i.e. 37 °C).

Practical Solution for Effective Whole-Body Magnetic Fluid Hyperthermia Treatment

Magnetic fluid hyperthermia therapy is considered as a promising treatment for cancers including unidentifiable metastatic cancers that are scattered across the whole body. However, a recent study on heat transfer simulated on a human body model showed a serious side effect: occurrences of hot spots in normal tissues due to eddy current loss induced by variation in the irradiated magnetic field. The indicated allowable upper limit of field amplitude Hac for constant irradiation over the entire human body corresponded to approximately 100 Oe at a frequency f of 25 kHz. The limit corresponds to the value Hacf of 2.5 × 106 Oe·s−1 and is significantly lower than the conventionally accepted criteria of 6 × 107 Oe·s−1. The present study involved evaluating maximum performance of conventional magnetic fluid hyperthermia cancer therapy below the afore-mentioned limit, and this was followed by discussing alternative methods not bound by standard frameworks by considering steady heat flow from equilibrium responses of stable nanoparticles. Consequently, the clarified potentials of quasi-stable core-shell nanoparticles, dynamic alignment of easy axes, and short pulse irradiation indicate that the whole-body magnetic fluid hyperthermia treatment is still a possible candidate for future cancer therapy.

Cancer cell extinction through a magnetic fluid hyperthermia treatment produced by superparamagnetic Co–Zn ferrite nanoparticles

TEG mediated synthesis of CZF MNPs for cancer cell extinction by using magnetic fluid hyperthermia therapy.

Analysis of the Distribution of Magnetic Fluid inside Tumors by a Giant Magnetoresistance Probe

Magnetic fluid hyperthermia (MFH) therapy uses the magnetic component of electromagnetic fields in the radiofrequency spectrum to couple energy to magnetic nanoparticles inside tumors. In MFH therapy, magnetic fluid is injected into tumors and an alternating current (AC) magnetic flux is applied to heat the magnetic fluid- filled tumor. If the temperature can be maintained at the therapeutic threshold of 42°C for 30 minutes or more, the tumor cells can be destroyed. Analyzing the distribution of the magnetic fluid injected into tumors prior to the heating step in MFH therapy is an essential criterion for homogenous heating of tumors, since a decision can then be taken on the strength and localization of the applied external AC magnetic flux density needed to destroy the tumor without affecting healthy cells. This paper proposes a methodology for analyzing the distribution of magnetic fluid in a tumor by a specifically designed giant magnetoresistance (GMR) probe prior to MFH heat treatment. Experimental results analyzing the distribution of magnetic fluid suggest that different magnetic fluid weight densities could be estimated inside a single tumor by the GMR probe.

Magnetic chitosan nanocomposite for hyperthermia therapy application: Preparation, characterization and in vitro experiments

Nanocrystals of magnetite (Fe3O4) were prepared by alkaline precipitation. The precursor used for synthesis was ferrous chloride only and the reaction was carried out in absence of any oxidant. The synthesized pure phase magnetic nanoparticles (MNPs) were coated with a biocompatible polymer, chitosan (CS). FTIR and TGA confirm coating of CS on MNPs. Both bare and coated MNPs (Fe3O4 and CS-Fe3O4) show particle size 21.8±5.3 and 15.1±5.0nm respectively. The magnetization values of both the MNPs are 51.68 and 49.96emu/g at room temperature respectively. Negligible Coercivity and Remenance values at room temperature imply superparamagnetic behavior of the MNPs. The MNPs are studied for their induction heating abilities at 167.6, 251.4 and 335.2Oe (equivalent to 13.3, 20.0 and 26.7kAm−1 respectively), in order to use them in magnetic fluid hyperthermia therapy. At 335.2Oe, CS coated nanoparticles (NPs) show maximum SAR of 118.85W/g, while bare NPs show SAR of 79.32W/g. Low cytotoxic effects of both the MNPs on L929 cell line proved their suitability for in vivo applications. NH2 group rendered by CS can further be used for conjugation of biomolecules to make them suitable candidates for biosensing and targeted drug delivery.

Magnetic core–shell structures for magnetic fluid hyperthermia therapy application

Nanocrystals of magnetite (Fe3O4) were prepared by alkaline precipitation. The precursor used for synthesis was ferrous chloride alone and the reaction was carried out in the absence of any oxidant. The synthesized pure phase magnetic nanoparticles (MNPs) were coated with a biocompatible polymer, acrypol (AP). Fourier transform infrared and thermogravimetric studies confirmed coating of AP on MNPs. Bare and coated MNPs (Fe3O4 and AP–Fe3O4) showed particle sizes of 21.8 ± 5.3 and 14.2 ± 5.0 nm respectively. The magnetization values of the MNPs were 37.77 and 32.71 emu g−1 at room temperature respectively. Negligible coercivity and remanence values at room temperature implied superparamagnetic behavior of the MNPs. The induction heating abilities of MNPs at 167.6, 251.4 and 335.2 Oe (equivalent to 13.3, 20.0 and 26.7 kA m−1 respectively) were studied, in order to use them in magnetic fluid hyperthermia therapy. At 335.2 Oe, AP coated NPs showed a maximum specific absorption rate (SAR) of 95.8 W g−1, while bare NPs showed a SAR of 74.4 W g−1. Zeta potential values of bare and coated MNPs were measured at a pH range from 2 to 10 in water. Both the colloidal suspensions were found to be very stable at extreme pH values. However, higher zeta potential values of coated MNPs were assigned to their higher colloidal stability. Low cytotoxic effects of both the MNPs on the L929 cell line proved their suitability for in vivo applications.

Design and Analysis of Novel Focused Hyperthermia Devices

Magnetic fluid hyperthermia (MFH) is a promising cancer therapy by virtue of its good depth penetration. As the injected magnetic fluids of MFH are inevitably distributed in the tumor as well as in normal tissues nearby, it is difficult to accurately heat and ablate the targeted tumor without damaging the surrounding healthy tissues. Based on the observation that magnetic nanoparticles are only heated by alternating fields and not by static dc fields, it is possible to exploit such findings in MFH therapy to provide an efficient cure for cancer patients. To avoid unnecessary heating of healthy tissues, a novel system is proposed to set up a dc magnetic field around the tumor target. At the same time, the system creates a field-free region (FFR) with negligible static magnetic field in the target area. The target area can then be fully heated by an alternating field whereas the nearby tissues are not heated. In this paper, a novel ac and dc magnetic field combined MFH system, targeting the treatment area, is presented to produce an accurately focused magnetic field to abate the tumor cells. The proposed method is validated using finite element analysis.

The use of magnetic nanoparticles in low frequency inductive hyperthermia

PurposeThe purpose of this paper is to present the basic ideas of magnetic nanoparticles' usage in the breast cancer treatment, which is called magnetic fluid hyperthermia. The proposed approach offers a relatively simple methodology of energy deposition, allowing an adequate temperature control at the target tissue, in this case a cancerous one. By means of a numerical method the authors aim to investigate two heating effects caused by varying magnetic fields, i.e. to compare the power density heating effects of eddy currents and magnetic nanoparticles.Design/methodology/approachIn order to numerically investigate the combination of the overheating effect of magnetic nanoparticles and eddy currents, the Finite Element Method solver based on FEniCS project has been prepared. To include the magnetic fluid in the model it has been assumed that power losses in the magnetic nanoparticles are completely converted into heat, according to experimentally developed formula. That formula can be interpreted as the hysteresis losses with regard to the volume of magnetic fluid. Finally, the total power density has been calculated as the product of the sum of power density from eddy currents and hysteresis losses. That methodology has been applied to calculate the effectiveness of magnetic fluid hyperthermia with regard to the female breast phantom.FindingsThe paper presents the methodology which can be used in magnetic fluid hyperthermia therapy planning and Computer Aid Diagnosis (CAD). Furthermore, it is shown how to overcome one of the most serious engineering challenges connected with hyperthermia, i.e. achieving adequate temperature in deep tumors without overheating the body surface.Practical implicationsThe obtained results connected with the assessment of eddy currents effect suggest that during hyperthermia treatment the configuration which consists of an exciting coil and human body, plays a curial role. Moreover, the authors believe that these results will help to predict the skin surface overheating that accompanies deep heating. The presented methodology can be used by engineers in the development of Computer Aid Diagnosis systems.Originality/valueIn a given patient's situation a number of choices must be made to determine the parameters of the hyperthermia treatment. These include the need of multiple‐point temperature measurements for accurate and thorough monitoring. Treatment planning will require accurate characterization of the applicator deposition pattern and the tissue parameters, as well as the numerical techniques to predict the resultant heating pattern. The presented paper shows how to overcome these problems from the numerical point of view at least.

Present status and prospects of magnetite nanoparticles-based hyperthermia

Magnetic fluid hyperthermia is a cancer treatment technique that utilizes the heat dissipated by magnetic nanoparticles exposed to an alternating current magnetic field. The heat dissipated is consequence of the conversion of the magnetic energy through different relaxation mechanisms, which depends on the physical properties of the magnetic particles. Particularly, in the case of magnetic nanoparticles, the magnetic energy is converted to heat energy either by the resistive response of the rotation of the magnetic particles (Brownian relaxation) or the rotation of the magnetic moment within the particles (Néel relaxation) to the alternating magnetic field. In this article, the main focus has been on the progress of theoretical and experimental investigations towards the realization of magnetic fluid hyperthermia (MFH) through heat dissipation by Néel relaxation of magnetite particles. We discuss about the present status and prospects of magnetite nanoparticles-based hyperthermia focusing mainly on the dissipation of heat through Néel relaxation mechanism. In doing so, an attempt has been made to review and deepen the understanding on specific topics such as (a) specific heat absorption characteristics of magnetite, especially the physical properties of particles that generate heat through Néel relaxation, (b) the preparation techniques available to synthesize particles with required properties, (c) experimental investigations carried out to determine the relative contribution of Néel relaxation to dissipate heat and their potential for in vivo application, and (d) the theoretical estimation of and experimental verification of heat diffusion characteristics of magnetite. The theoretical and experimental studies have suggested that the development of case specific treatment technologies based on an integrated approach considering both the physical constraints of the magnetic particles to be used as thermal seeds and practically feasible alternating magnetic field generators is a must for the establishment of MFH therapy in the foreseeable future.

Post-mortem studies in glioblastoma patients treated with thermotherapy using magnetic nanoparticles

Patients with glioblastoma multiforme (GBM), the most common primary brain tumor in adults, have still a poor prognosis though new strategies of radio- and chemotherapy have been developed. Recently, our group demonstrated the feasibility, tolerability and anti-tumoral effects of a newly developed therapeutic approach, termed thermotherapy using magnetic nanoparticles or magnetic fluid hyperthermia (MFH), in a murine model of malignant glioma. Currently, the efficacy of MFH is being evaluated in a phase II study. Here, we report on post-mortem neuropathological findings of patients with GBM receiving MFH. In brain autopsies the installed magnetic nanoparticles were dispersed or distributed as aggregates within geographic tumor necroses, restricted in distribution to the sites of instillation. Therefore, our results underscore the need for multiple trajectories of instillation. The typical GBM necrosis with pseudopalisading was free of particles. Dispersed particles and particle aggregates were phagocytosed mainly by macrophages whereas glioblastoma cells showed an uptake to a minor extent. MFH therapy further promotes uptake of nanoparticles in macrophages, likely as a consequence of tumor inherent and therapy induced formation of necrosis with subsequent infiltration and activation of phagocytes. We did not observe bystander effects of MFH such as sarcomatous tumour formation, formation of a sterile abscess or foreign body giant cell reaction. Furthermore, all patients did not present any clinical symptoms related to possible adverse effects of MFH.