Magnetic Fluid Hyperthermia Treatment Research Articles

A Novel Local Magnetic Fluid Hyperthermia Based on High Gradient Field Guided by Magnetic Particle Imaging.

Magnetic Particle Imaging (MPI)-guided Magnetic Fluid Hyperthermia (MFH) has the potential for widespread utilization, as it allows for the prediction of magnetothermal dosage, real-time visualization of the thermal therapy process, and precise localization of the lesion area. However, the existing MPI-guided MFH (MPI-MFH) method is insensitive to concentration gradients of magnetic nanoparticles (MNPs) and is susceptible to causing damage to normal tissues with high MNP concentrations during MFH treatment, while inadequately heating tumor tissues with lower MNP concentrations. In this work, we established a relationship between MNP concentration and heating efficiency through simulations and phantom measurements, enabling the optimal selection of MFH parameters guided by MPI. Based on these findings, we developed a high-gradient field MPI-MFH method using a field-free point (FFP) approach to achieve precise local heating. Phantom experiments and in vivo glioma model experiments were conducted to validate this proposed method. The results demonstrated that the proposed method of MPI-MFH can improve the MNP concentration gradient sensitivity to ±1 mg/ml, thereby enabling more effective lesion-site heating without damaging normal tissues. This method not only reduced glioma size effectively but also holds promise for application in various other types of cancers.

Magnetic Nanoparticles in Cancer Thermotherapy: A Mathematical Approach to Optimal Treatment Design

Thermotherapy, often called Hyperthermia treatment is a cancer treatment modality that involves raising the temperature of the tumor mass to over 315 K (42°C) for a specific duration, which leads to cell death through apoptosis or necrosis. Magnetic Particle Hyperthermia (MPH) is a non-invasive technique where magnetic nanoparticles are introduced into the tumor and then exposed to a magnetic field which convert magnetic energy into heat. Due to their high acidity, tumor cells are more sensitive to heat than healthy cells, meaning that heating the tumor to 315-319 K (42°C–46°C) can destroy it with minimal damage to the surrounding healthy tissues. During hyperthermia treatment, blood perfusion helps protect the healthy tissues around the tumor by dissipating excess heat. This paper presents a study where the temperature profiles within a spherical hepatic tumor mass are estimated by solving Pennes’ Bio-heat Equation, incorporating a power term. The study uses analytical methods to examine the effects of magnetic fluid hyperthermia treatment. Numerical illustrations are carried out using magnetite (Fe3O4) nanoparticles having an average diameter of 10.9 nm with mineral oil as a carrier liquid, subjected to magnetic fields of varying intensities. By analysing the model, the present work helps in designing an optimal treatment protocol by identify the time threshold of the therapy for varying magnetic field strengths.

Doped Ferrite Nanoparticles Exhibiting Self-Regulating Temperature as Magnetic Fluid Hyperthermia Antitumoral Agents, with Diagnostic Capability in Magnetic Resonance Imaging and Magnetic Particle Imaging.

Simple SummaryHyperthermia, a limited increase in tumor tissue temperature up to a maximum of 45 °C, has long been used in cancer treatment, either as a stand-alone therapy or in conjunction with chemo-/radiotherapy. Among the different physical procedures used, a particularly promising technique is magnetic fluid hyperthermia (MFH): this consists of the local administration of magnetic nanoparticles, followed by the application of alternating magnetic fields. One concern with this technique is the possibility of damage to healthy peritumoral tissue. The present study investigates innovative nanoparticles with self-regulating temperature, which should reduce this risk and thus mark a significant step forward in MFH. In an experimental model of aggressive breast cancer, we demonstrated a substantial reduction of tumor growth rate by using an experimental MFH protocol, transferable to clinical practice. These innovative nanomaterials present the added advantage of allowing non-invasive monitoring of temperature, by magnetic resonance imaging (MRI) and magnetic particle imaging (MPI).This paper reports a comprehensive investigation of a magnetic nanoparticle (MNP), named M55, which belongs to a class of innovative doped ferrite nanomaterials, characterized by a self-limiting temperature. M55 is obtained from M48, an MNP previously described by our group, by implementing an additional purification step in the synthesis. M55, after citrate and glucose coating, is named G-M55. The present study aimed to demonstrate the properties of G-M55 as a diagnostic contrast agent for MRI and magnetic particle imaging (MPI), and as an antitumoral agent in magnetic fluid hyperthermia (MFH). Similar specific absorption rate values were obtained by standard MFH and by an MPI apparatus. This result is of interest in relation to the application of localized MFH by MPI apparatus. We demonstrated the biocompatibility of G-M55 in a triple-negative human breast cancer line (MDA-MB-231), and its efficacy as an MFH agent in the same cell line. We also demonstrated the efficacy of MFH treatment with G-M55 in an experimental model of breast cancer. Overall, our results pave the way for the clinical application of G-M55 as an MFH agent in breast cancer therapy, allowing not only efficient treatment by both standard MFH apparatus and MPI but also temperature monitoring.

Synthesis, Characterization and Hyperthermic Evaluation of PEGylated Superparamagnetic MnFe2O4 Ferrite Nanoparticles for Cancer Therapeutics Applications

AbstractPoly(ethylene glycol) (PEG)‐coated superparamagnetic MnFe2O4 ferrite nanoparticles are of great interest for application in magnetic fluid hyperthermia (MFH) due to their heat generation capability in an external alternating magnetic field, besides biocompatibility, and surface properties. MFH has emerged as a promising therapeutic approach for cancer treatment and is based on controlled heating tumor tissue through the accumulation of MnFe2O4 ferrite nanoparticles within cancer cells. In the present work, MnFe2O4 superparamagnetic ferrite nanoparticles via the chemical combustion method are synthesized. The preparation of PEGylated MnFe2O4 ferrite nanoparticles, which involves the attachment of such molecules at the surface, without the need for coupling agents or prior modification on the species involved. The conjugation of folate onto MnFe2O4 ferrite nanoparticles is confirmed by FTIR spectroscopy. The MnFe2O4 ferrite nanoparticles are colloidal stable. The obtained targeted PEGylated MnFe2O4 ferrite nanoparticles show superparamagnetic behavior with a saturation magnetization of 78.68 emu·g−1 at 300 K. Their specific absorption rate (SAR) ranged from 43.2 to 19.5 W g−1 in an alternating magnetic field of 5—20 kA m−1. The heat generated is sufficient to raise the sample temperature to the therapeutic range used in MFH establishing this system as promising candidates for use in MFH treatment.

Magnetically guided theranostics: montmorillonite-based iron/platinum nanoparticles for enhancing in situ MRI contrast and hepatocellular carcinoma treatment

In Asia, including Taiwan, malignant tumors such as Hepatocellular carcinoma (HCC) one of the liver cancer is the most diagnosed subtype. Magnetic resonance imaging (MRI) has been a typical diagnostic method for accurately diagnosing HCC. When it is difficult to demonstrate non-enhanced MRI of tumors, radiologists can use contrast agents (such as Gd3+, Fe3O4, or FePt) for T1-weighted and T2-weighted imaging remain in the liver for a long time to facilitate diagnosis via MRI. However, it is sometimes difficult for T2-weighted imaging to detect small tumor lesions because the liver tissue may absorb iron ions. This makes early cancer detection a challenging goal. This challenge has prompted current research to create novel nanocomposites for enhancing the noise-to-signal ratio of MRI. To develop a method that can more efficiently diagnose and simultaneously treat HCC during MRI examination, we designed a functionalized montmorillonite (MMT) material with a porous structure to benefit related drugs, such as mitoxantrone (MIT) delivery or as a carrier for the FePt nanoparticles (FePt NPs) to introduce cancer therapy. Multifunctional FePt@MMT can simultaneously visualize HCC by enhancing MRI signals, treating various diseases, and being used as an inducer of magnetic fluid hyperthermia (MFH). After loading the drug MIT, FePt@MMT-MIT provides both MFH treatment and chemotherapy in one nanosystem. These results ultimately prove that functionalized FePt@MMT-MIT could be integrated as a versatile drugs delivery system by combining with MRI, chemotheraeutic drugs, and magnetic guide targeting.

Magnetic Fluid Hyperthermia as Treatment Option for Pancreatic Cancer Cells and Pancreatic Cancer Organoids.

IntroductionPancreatic ductal adenocarcinoma (PDAC) is a cancer with a meager prognosis due to its chemotherapy resistance. A new treatment method may be magnetic fluid hyperthermia (MFH). Magnetoliposomes (ML), consisting of superparamagnetic iron oxide nanoparticles (SPION) stabilized with a phospholipid-bilayer, are exposed to an alternating magnetic field (AMF) to generate heat. To optimize this therapy, we investigated the effects of MFH on human PDAC cell lines and 3D organoid cultures.Material and MethodsML cytotoxicity was tested on Mia PaCa-2 and PANC-1 cells and on PDAC 3D organoid cultures, generated from resected tissue of patients. The MFH was achieved by AMF application with an amplitude of 40–47 kA/m and a frequency of 270 kHz. The MFH effect on the cell viability of the cell lines and the organoid cultures was investigated at two different time points. Clonogenic assays evaluated the impairment of colony formation. Altering ML set-ups addressed differences arising from intra- vs extracellular ML locations.ResultsMia PaCa-2 and PANC-1 cells showed no cytotoxic effects at ML concentrations up to 300 µg(Fe)/mL and 225 µg(Fe)/mL, respectively. ML at a concentration of 225 µg(Fe)/mL were also non-toxic for PDAC organoid cultures. MFH treatment using exclusively extracellular ML presented the highest impact on cell viability. Clonogenic assays demonstrated remarkable impairment as long-term outcome in MFH-treated PDAC cell lines. Additionally, we successfully treated PDAC organoids with extracellular ML-derived MFH, resulting in notably reduced cell viabilities 2h and 24 h post treatment. Still, PDAC organoids seem to partly recover from MFH after 24 h as opposed to conventional 2D-cultures.ConclusionTreatment with MFH strongly diminished pancreatic cancer cell viability in vitro, making it a promising treatment strategy. As organoids resemble the more advanced in vivo conditions better than conventional 2D cell lines, our organoid model holds great potential for further investigations.

Micron-sized iron oxide particles for both MRI cell tracking and magnetic fluid hyperthermia treatment

Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF). Micrometric IOP have a high sensitivity of detection. Nevertheless, little is known about their internalization processes or their potential heat power. Two micrometric commercial IOP (from Bangs Laboratories and Chemicell) were characterized by Transmission Electron Microscopy (TEM) and their endocytic pathways into glioma cells were analyzed. Their Specific Absorption Rate (SAR) and cytotoxicity were evaluated using a commercial AMF inductor. T2-weighted imaging was used to monitor tumor growth in vivo after MFH treatment in mice. The two micron-sized IOP had similar structures and r2 relaxivities (100 mM−1 s−1) but involved different endocytic pathways. Only ScreenMAG particles generated a significant rise in temperature following AMF (SAR = 113 W g−1 Fe). After 1 h of AMF exposure, 60% of ScreenMAG-labeled cells died. Translated to a glioma model, 89% of mice responded to the treatment with smaller tumor volume 42 days post-implantation. Micrometric particles were investigated from their characterization to their intracellular internalization pathways and applied in one in vivo cancer treatment, i.e. MFH.

Extracellular and intracellular intermittent magnetic-fluid hyperthermia treatment of SK-Hep1 hepatocellular carcinoma cells based on magnetic nanoparticles coated with polystyrene sulfonic acid.

The use of magnetic nanoparticles (MNPs) magnetized on applying an alternating magnetic field (AMF) to stimulate the thermal characteristics and to induce tumor apoptosis is a currently active area of research in cancer treatment. In previous work, we developed biocompatible and superparamagnetic polystyrene-sulfonic-acid-coated magnetic nanoparticles (PSS-MNPs) as applications for magnetically labeled cell trapping, but without assessment of treatment effects on tumor diseases. In the present work, we examined PSS-MNP-induced magnetic fluid hyperthermia (MFH) on SK-Hep1 hepatocellular carcinoma (HCC) cells for lethal thermal effects with a self-made AMF system; an adjustable AMF frequency generated a variable intensity of magnetic field and induced MNP relaxation. The extracellular and intracellular MFH treatments on a SK-Hep1 cell line were implemented in vitro; the result indicates that the lethal effects were efficient and caused a significantly decreased cell viability of SK-Hep1 cells. As the PSS-MNP concentration decreased, especially in intracellular MFH treatments, the MFH effects on cells, however, largely decreased through heat spreading to the culture medium. On controlling and decreasing the volume of culture medium, the problem of heat spreading was solved. It can be consequently expected that PSS-MNPs would be a prospective agent for intracellular cancer magnetotherapy.

3D in silico study of magnetic fluid hyperthermia of breast tumor using Fe3O4 magnetic nanoparticles.

Modeling and simulation of the temperature distribution, the mass concentration, and the heat transfer in the breast tissue are hot issues in magnetic fluid hyperthermia treatment of cancer. The breast tissue can be visualized as a porous matrix with saturated blood. In this paper, 3D in silico study of breast cancer hyperthermia using magnetic nanoparticles (MNPs) is conducted. The 3D FEM models are incorporated to investigate the infusion and backflow of nanofluid in the breast tumor, the diffusion of nanofluid, temperature distribution during the treatment, and prediction of the fraction of tumor necrosis while dealing with the thermal therapy. All the hyperthermia procedures are simulated and analyzed on COMSOL Multiphysics. The sensitivity of frequency and amplitude of the applied magnetic field (AMF) is investigated on the heating effect of the tumor. The mesh dependent solution of Penne's bioheat model is also analyzed. The simulated results demonstrate successful breast cancer treatment using MNPs with minimum side effects. Validation of current simulations results with experimental studies existing in literature advocates the success of our therapy. The increase in the amplitude and frequency of the AMF increases of the temperature in the tumor. The variation of mesh from coarser to finer increased the temperature through small fractions. We have also simulated the magnetic induction problem where the magnetic field is generated by current-carrying coil conductors induce heat in nearby breast tumors due to excitation of MNPs by magnetic flux. This research will aid treatment protocols and real-time clinical breast cancer treatments.

PEGlatyon-SPION surface functionalization with folic acid for magnetic hyperthermia applications

Superparamagnetic iron oxide nanoparticles (SPION) are of great interest for application in magnetic fluid hyperthermia (MFH) due to their heat generation capability in an external alternating magnetic field, besides biocompatibility, and surface properties. MFH has emerged as a promisor therapeutic approach for cancer treatment and is based in controlled heating tumor tissue through the accumulation of SPIONs within cancer cells. This work describes a new route for the preparation of folate-conjugated PEGylated SPIONs, which involves the attachment of such molecules at the surface through polycondensation reactions, without the need for coupling agents or prior modification on the species involved. The size of iron oxide cores obtained by transmission electron microscopy was about 12 nm. The conjugation of folate onto SPIONs was confirmed by FTIR spectroscopy. The folate conjugated nanoparticles were colloidal stable in PBS, presenting a hydrodynamic diameter of 109 ± 1 nm and PDI 0.148. The obtained folate-targeted PEGylated SPIONs showed superparamagnetic behavior with a saturation magnetization of 73.1 emu·g−1 at 300 K. Their specific absorption rate (SAR) ranged from 32.8 to 15.0 W g−1 in an alternating magnetic field of 10–16 kA m−1 and frequency of 420–203 kHz. The heat generated was sufficient to raise the sample temperature to the therapeutic range used in MFH establishing this system as promising candidates for use in MFH treatment.

Magnetic stimulation of gold fiducial markers used in Image-Guided Radiation Therapy: Evidences of hyperthermia effects

A promising approach in oncology consists in combining Radiation Therapy (RT) with Magnetic Fluid Hyperthermia (MFH). Modern day RT takes advantage by imaging techniques able to provide information about the correct patient set-up, target position and movement during the treatments. For these purposes, gold fiducial markers, implanted into the tumors, or in their proximity, are used in the so-called Image-Guided Radiation Therapy (IGRT).In this study, hyperthermia produced by different gold fiducial markers under the application of an alternating magnetic field in the typical conditions used in Magnetic Fluid Hyperthermia (MFH) clinical trials was investigated. The temperature increase of different types of gold fiducial markers and of tissue mimicking hydrogel phantoms containing the fiducials were measured during the magnetic stimulation by means of a high-resolution thermal camera and a fiber optic temperature sensor.The results demonstrated that, within few tens of seconds after the start of the magnetic stimulation, the gold fiducial markers might reach temperatures higher than 70 °C. Local increases of the hydrogel temperature to values higher than 45 °C were also measured. These evidences highlight the need to evaluate carefully the presence and location of gold fiducial markers in patients undergoing combined IGRT and MFH treatments in order to prevent any thermal ablation of health tissues surrounding the markers.

Evaluation of magnetic nanoparticles for magnetic fluid hyperthermia

Background: Magnetic nanoparticles (MNPs) generate heat when exposed to an alternating magnetic field. Consequently, MNPs are used for magnetic fluid hyperthermia (MFH) for cancer treatment, and have been shown to increase the efficacy of chemotherapy and/or radiation treatment in clinical trials. A downfall of current MFH treatment is the inability to deliver sufficient heat to the tumor due to: insufficient amounts of MNPs, unequal distribution of MNPs throughout the tumor, or heat loss to the surrounding environment.Objective: In this study, the objective was to identify MNPs with high heating efficiencies quantified by their specific absorption rate (SAR).Methods: A panel of 31 commercially available MNPs were evaluated for SAR in two different AMFs. Additionally, particle properties including iron content, hydrodynamic diameter, core diameter, magnetic diameter, magnetically dead layer thickness, and saturation mass magnetization were investigated.Results: High SAR MNPs were identified. For SAR calculations, the initial slope, corrected slope, and Box–Lucas methods were used and validated using a graphical residual analysis, and the Box–Lucas method was shown to be the most accurate. Other particle properties were identified and examined for correlations with SAR values. Positive correlations of particle properties with SAR were found, including a strong correlation for the magnetically dead layer thickness.Conclusions: This work identified high SAR MNPs for hyperthermia, and provides insight into properties which correlate with SAR which will be valuable for synthesis of next-generation MNPs. SAR calculation methods must be standardized, and this work provides an in-depth analysis of common calculation methods.

261. Hyperthermia properties of gold fiducial markers

Purpose The combination of Radiotherapy and Magnetic Fluid Hyperthermia (MFH) is gaining importance since it may offer new strategies for several oncological pathologies. In MFH magnetic nanoparticles are injected directly into the tumour and, under the action of an externally applied alternating magnetic field HAC, they generate an amount of heat proportional to the field. Metallic materials implanted within 40 cm from the tumour heat up during MFH treatment and are removed. The aim of this work is to investigate the hyperthermia properties of the fiducial markers employed in Image Guided Radiation Therapy (IGRT) and to study the physics mechanisms of the observed macroscopic effects. Methods and materials Hydrogel matrix samples were prepared and used as tissue mimicking materials. Different types of gold fiducial markers used in IGRT procedures were positioned in gel samples, considering various geometric configurations simulating the actual position of the markers in the clinical practice. Hyperthermic properties of gold fiducial markers were studied varying the field amplitude HAC from 7 to 17 kA/m and the frequency from 100 to 1000 kHz. During the stimulation, an optical fiber based sensor enables the measurement of the temperature in a point of the hydrogel samples. Beside these temperature measurement, a high-resolution thermal camera was used to map the temperature distribution over the samples. Results Preliminary results attested an increase of the temperature in the gel matrices as effect of the heating of the gold fiducial markers under a suitable magnetic stimulation. Hyperthermic effects were also significant in the typical experimental conditions (2 Conclusion The results of this study highlight the need to carefully evaluate the presence and location of gold fiducial markers in patients undergoing MFH treatments, in order to prevent damage to health tissues surrounding the lesions.

In-gel study of the effect of magnetic nanoparticles immobilization on their heating efficiency for application in Magnetic Fluid Hyperthermia

Abstract Recent studies on magnetic nanoparticles (MNPs) used for Magnetic Fluid Hyperthermia treatments have shown that Brownian rotation is suppressed when they are confined within a cell. To investigate this effect we conducted a systematic study of the Specific Absorption Rate (SAR) of colloidal suspensions of MNPs in water and gels at different agarose concentration. SAR measurements were conducted by varying the frequency (f = 110–990 kHz) and amplitude (up to 17 kA/m) of the applied alternating magnetic field (AMF). MNP samples with different diameter (d = 10, 14, and 18 nm) were used. Our results show that Neel relaxation dominates SAR with negligible contribution from Brownian motion for smaller MNPs (d = 10 nm). For the largest MNPs (d = 18 nm) we observed a more significant SAR decrease in gel suspensions as compared to those in solution. In particular, when applying AMFs as the ones used in a clinical setting (16.2 kA/m at f = 110 kHz), we measured SAR value of 67 W/g in solution and 25 W/g in gel. This experimental finding demonstrates that investigation of MNPs properties should be conducted in media with viscosity similar to the one found in mammalian tissues.

Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells

Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells.

A superparamagnetic metallopolymer using tailor-made poly[2-(acetoacetoxy)ethyl methacrylate] bearing pendant β-keto ester functionality

Poly[2-(acetoacetoxy)ethyl methacrylate] (PAEMA), a functional polymer bearing pendant β-keto ester group was prepared via atom transfer radical polymerization (ATRP). The polymers were characterized by 1H NMR, GPC and DSC analyses. 1H NMR analysis showed that β-keto ester group present in the side chain of the PAEMA was more in the keto form as compared to the enol form. The reactive pendant β-keto ester group of PAEMA reacted with cobalt(II) ion to form metallopolymer which was characterized by FT-IR, UV–vis, TGA, DSC, FESEM and TEM analyses. This cobalt-polymer complex showed the formation of nanogel, as observed by DLS analysis. Importantly, this cobalt-polymer complex showed superparamagnetic behavior, as observed via superconducting quantum interference device (SQUID) analysis, indicating its potential application in magnetic fluid hyperthermia treatment and radiotherapy.

Biomass-based magnetic fluorescent nanoparticles: One-step scalable synthesis, application as drug carriers and mechanism study

A biomass-based magnetic fluorescent nanoparticle (MFNPs) was successively in situ synthesized via a one-step high-gravity approach, which constructed by a magnetic core of Fe3O4 nanoparticles, the fluorescent marker of carbon dots (CDs), and shells of chitosan (CS). The obtained MFNPs had a 10 nm average diameter and narrow particle size distribution, low cytotoxicity, superior fluorescent emission and superparamagnetic properties. The encapsulating and release 5-fluorouracil experiments confirmed that the introduction of CS/CDs effectively improved the drug loading capacity. Mechanism and kinetic studies proved that: (i) the monolayer adsorption was the main sorption mode under the studied conditions; (ii) the whole adsorption process was controlled by intra-liquid diffusion mass transfer and governed by chemisorption; and (iii) the release process was controlled by Fickian diffusion. These results demonstrated this method to one-step continuously produce MFNPs and the construction of non-toxic nanostructure possessed great superiority in currently Nano-delivery systems, which would show high application value in targeted drug delivery, magnetic fluid hyperthermia treatment, magnetic resonance imaging (MRI), in vitro testing and relative research.

HSP70 Inhibition Synergistically Enhances the Effects of Magnetic Fluid Hyperthermia in Ovarian Cancer.

Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43°C, which revealed that heat shock protein (HSP) genes, including HSPA6, were upregulated. HSPA6 encodes the Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70-related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect. In vivo efficacy experiments with HSPA6 siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer. Mol Cancer Ther; 16(5); 966-76. ©2017 AACR.

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.

A study on DPL model of heat transfer in bi-layer tissues during MFH treatment

In this paper, dual-phase-lag bioheat transfer model subjected to Fourier and non-Fourier boundary conditions for bi-layer tissues has been solved using finite element Legendre wavelet Galerkin method (FELWGM) during magnetic fluid hyperthermia. FELWGM localizes small scale variation of solution and fast switching of functional bases. It has been observed that moderate hyperthermia temperature range (41–46°C) can be better achieved in spherical symmetric coordinate system and treatment method will be independent of the Fourier and non-Fourier boundary conditions used. The effect of phase-lag times has been observed only in tumor region. FCC FePt magnetic nano-particle produces more effective treatment with respect to other magnetic nano-particles. The effect of variability of magnetic heat source parameters (magnetic induction, frequency, diameter of magnetic nano-particles, volume fractional of magnetic nano-particles and ligand layer thickness) has been investigated. The physical property of these parameters has been described in detail during magnetic fluid hyperthermia (MFH) treatment and also discussed the clinical application of MFH in Oncology.