Application In Hyperthermia Therapy Research Articles

An Ultra-small Heated Area Masked Microwave Hyperthermia Therapy Scheme in Fresnel Region

This paper introduces a localized masked thermal therapy method for only the breast through the Fresnel region. A pyramidal horn antenna has been used as a hyperthermia system applicator. The antenna is fed by a Yagi array and resonates at 4.74 GHz. A metal plate with a square slot masked the breast phantom. The antenna irradiates the breast phantom for 5 and 10 minutes with input power of 10 and 20 watts (W). Thermal and specific absorption rate (SAR) distributions are studied under the same conditions for a fair comparison between masked and unmasked system performance. The square slot dimensions are altered, and their effects are studied considering the phantom heated area. Moving from unmasked to masked hyperthermia scenarios, a heated area size reduction of 99.87 % is achieved along with a very considerable SAR value reduction. The masked scenario elevates the breast temperature to 43 C∘ in a very concentrated area. The proposed system can elevate only an area of 2×2mm2 of the breast tissue to a temperature of 40 C∘ in 5 minutes, and that is a very promising result in hyperthermia therapy applications.

Magnetic Nanoparticles as Mediators for Magnetic Hyperthermia Therapy Applications: A Status Review

This concise review delves into the realm of superparamagnetic nanoparticles, specifically focusing on Fe2O3, Mg1+xFe2−2xTixO4, Ni1−xCux, and CrxNi1−x, along with their synthesis methods and applications in magnetic hyperthermia. Remarkable advancements have been made in controlling the size and shape of these nanoparticles, achieved through various synthesis techniques such as coprecipitation, mechanical milling, microemulsion, and sol–gel synthesis. Through this review, our objective is to present the outcomes of diverse synthesis methods, the surface treatment of superparamagnetic nanoparticles, their magnetic properties, and Curie temperature, and elucidate their impact on heating efficiency when subjected to high-frequency magnetic fields.

Systematically Designed Surface and Morphology of Magnetite Nanoparticles Using Monocarboxylic Acid with Various Chain Lengths under Hydrothermal Condition.

Hydrothermal synthesis of surface-modified magnetite nanoparticles (NPs) was performed in a batch reactor at 200 °C for 20 min while using monocarboxylic acid with various alkyl chain lengths (C6 to C18) as surface modifiers. The short-chain cases (C6 to C12) successfully gave the surface-modified NPs with uniform shape and magnetite structure, while the long-chain cases (C14 to C18) gave the NPs with nonuniform shape and two structures (magnetite and hematite). Additionally, the synthesized NPs were revealed to have single crystallinity, high stability, and ferromagnetic property, which were useful for hyperthermia therapy via various characterization techniques. These investigations would guide the selection guidelines for a surface modifier to control the structure, surface, and magnetic properties of surface-modified magnetite NPs with high crystallinity and stability, particularly for hyperthermia therapy applications.

Fe<sub>3</sub>O<sub>4</sub> Nanoparticles Prepared by Coprecipitations Method for Hyperthermia Therapy

Magnetic nanoparticles (Fe3O4) have considerable attention in various biomedical applications such as biosensors, drug delivery systems in the body, magnetic resonance imaging (MRI), and hyperthermia therapy. Hyperthermia therapy uses heat controlled by applied AC (Alternating Current) magnetic to kill cancer cells. This research aims to determine the effect of changes in temperature caused by the AC magnetic field on the varied magnetic nanoparticle solution. The Synthesize of Fe3O4 used the coprecipitation method to produce Fe3O4 nanoparticles. Mass of Fe3O4 nanoparticles varied of 95 mg and 125 mg. Nanoparticles physical properties were characterized using X-ray diffraction (XRD), Scanning Electron Microscope (SEM), and vibrating sample magnetometer (VSM). XRD profiles indicated that magnetic (Fe3O4) nanoparticles were successfully synthesized with a crystal size of 7.76 nm. SEM characterization of Fe3O4 nanoparticles was carried out at a magnification of 150.000 times and the average diameter of Fe3O4 powder nanoparticles was 20 nm. The temperature change measurement was performed using an AC magnetic field of 2.8 mT and frequency of 343 Hz, and time recorded changes temperature in 660 seconds. The temperature changes for solution concentrations of 95 mg and 125 mg were 7.7°C and 9.8°C, respectively. the concentration of solutions affects the value of the Specific Absorption Rate (SAR). The SAR values of each concentration of Fe3O4 solution were 0,0069 W/g and 0.0096 W/g. It proves that Fe3O3 prepared by coprecipitation method has potential for hyperthermia therapy application.

Immobilization of protein on Fe3O4 nanoparticles for magnetic hyperthermia application

We report a facile approach for the preparation of protein conjugated glutaric acid functionalized Fe3O4 magnetic nanoparticles (Pro-Glu-MNPs), having improved colloidal stability and heating efficacy. The Pro-Glu-MNPs were prepared by covalent conjugation of BSA protein onto the surface of glutaric acid functionalized Fe3O4 magnetic nanoparticles (Glu-MNPs) obtained through thermal decomposition. XRD and TEM analyses confirmed the formation of crystalline Fe3O4 nanoparticles of average size ~5 nm, whereas the conjugation of BSA protein to them was evident from XPS, FTIR, TGA, DLS and zeta-potential measurements. These Pro-Glu-MNPs showed good colloidal stability in different media (water, phosphate buffer saline, cell culture medium) and exhibited room temperature superparamagnetism with good magnetic field responsivity towards the external magnet. The induction heating studies revealed that the heating efficacy of these Pro-Glu-MNPs was strongly reliant on the particle concentration and their stabilizing media. In addition, they showed enhanced heating efficacy over Glu-MNPs as surface passivation by protein offers colloidal stability to them as well as prevents their aggregation under AC magnetic field. Further, Pro-Glu-MNPs are biocompatible towards normal cells and showed substantial cellular internalization in cancerous cells, suggesting their potential application in hyperthermia therapy.

Lissajous scanning magnetic particle imaging as a multifunctional platform for magnetic hyperthermia therapy.

The use of engineered nanoscale magnetic materials in healthcare and biomedical technologies is rapidly growing. Two examples which have recently attracted significant attention are magnetic particle imaging (MPI) for biological monitoring, and magnetic field hyperthermia (MFH) for cancer therapy. Here for the first time, the capability of a Lissajous scanning MPI device to act as a standalone platform to support the application of MFH cancer treatment is presented. The platform is shown to offer functionalities for nanoparticle localization, focused hyperthermia therapy application, and non-invasive tissue thermometry in one device. Combined, these capabilities have the potential to significantly enhance the accuracy, effectiveness and safety of MFH therapy. Measurements of nanoparticle hyperthermia during protracted exposure to the MPI scanner's 3D imaging field sequence revealed spatially focused heating, with a maximum that is significantly enhanced compared with a simple 1-dimensional sinusoidal excitation. The observed spatial heating behavior is qualitatively described based on a phenomenological model considering torques exerted in the Brownian regime. In vitro cell studies using a human acute monocytic leukemia cell line (THP-1) demonstrated strong suppression of both structural integrity and metabolic activity within 24 h following a 40 min MFH treatment actuated within the Lissajous MPI scanner. Furthermore, reconstructed MPI images of the nanoparticles distributed among the cells, and the temperature-sensitivity of the MPI imaging signal obtained during treatment are demonstrated. In summary, combined Lissajous MPI and MFH technologies are presented; demonstrating for the first time their potential for cancer treatment with maximum effectiveness, and minimal collateral damage to surrounding tissues.

Encapsulation of superparamagnetic iron oxide nanoparticles with polyaspartamide biopolymer for hyperthermia therapy

We report a delicate synthesis process of polyaspartamide-encapsulated superparamagnetic iron oxide nanoparticles (PA-encapsulated SPIONs) with their sufficiently obtained grain-size below 100 nm for hyperthermia application. Iron oxide nanoparticles with a high magnetization have been applied as nano-heaters while polyaspartamide (PA) is a biocompatible and biodegradable polymer with a polysuccinimide (PSI) backbone. Multi-functional polymer PA could be conjugated with other groups such as biotin to enhance the uptake capability by receptors of cancer cells. Consequently, encapsulating SPIONs nano-heaters with PA biopolymer is an attractive roadmap for hyperthermia therapy application. Our results revealed that PA-encapsulated SPIONs showed excellent biocompatible behavior based on cell viability test. With Prussian blue staining of cancer cells (4T1), cellular uptake of PA-encapsulated SPIONs was significantly increased in the presence of biotin conjugated on the outer shell. Furthermore, PA-encapsulated SPIONs exhibited effective cancer killing activities in both in vitro and in vivo hyperthermia experiments. Therefore, PA-encapsulated SPIONs might have potential for hyperthermia therapy.

Magnetic domain interactions of Fe3O4 nanoparticles embedded in a SiO2 matrix

Currently, superparamagnetic functionalized systems of magnetite (Fe3O4) nanoparticles (NPs) are promising options for applications in hyperthermia therapy, drug delivery and diagnosis. Fe3O4 NPs below 20 nm have stable single domains (SSD), which can be oriented by magnetic field application. Dispersion of Fe3O4 NPs in silicon dioxide (SiO2) matrix allows local SSD response with uniaxial anisotropy and orientation to easy axis, 90° <001> or 180° <111>. A successful, easy methodology to produce Fe3O4 NPs (6–17 nm) has been used with the Stöber modification. NPs were embedded in amorphous and biocompatible SiO2 matrix by mechanical stirring in citrate and tetraethyl orthosilicate (TEOS). Fe3O4 NPs dispersion was sampled in the range of 2–12 h to observe the SiO2 matrix formation as time function. TEM characterization identified optimal conditions at 4 h stirring for separation of SSD Fe3O4 in SiO2 matrix. Low magnetization (Ms) of 0.001 emu and a coercivity (Hc) of 24.75 Oe indicate that the embedded SSD Fe3O4 in amorphous SiO2 reduces the Ms by a diamagnetic barrier. Magnetic force microscopy (MFM) showed SSD Fe3O4 of 1.2 nm on average embedded in SiO2 matrix with uniaxial anisotropy response according to Fe3+ and Fe2+ electron spin coupling and rotation by intrinsic Neél contribution.

Structural analysis and magnetic induced hyperthermia of Fe3+and Mn2+substituted β-Ca3(PO4)2

Fe3+/Mn2+co-substitutions in β-Ca3(PO4)2elicit a good hyperthermia effect and biocompatible features.

On-demand drug release and hyperthermia therapy applications of thermoresponsive poly-(NIPAAm-co-HMAAm)/polyurethane core-shell nanofiber mat on non-vascular nitinol stents

A functional cover made up of core-shell nanofibers with a unique combination of thermoresponsive polymeric shell and stretchable polymeric core for non-vascular nitinol stents that uses an alternating magnetic field (AMF) to induce heat in the stent for hyperthermia therapy and simultaneously release 5-fluorouracil and/or paclitaxel was designed. Varying the ratios of NIPAAm to HMAAm monomer resulted in different LCST properties for the synthesized copolymer and further utilized for an on-demand drug release. Biocompatibility test using NIH-3T3 fibroblast cells indicates that the composite with drug content is biocompatible and the in-vitro cancer cytotoxicity test using ESO26 and OE21 cancer cells proved that the material shows cancer cytotoxic properties via combination of dual drug and hyperthermia therapy. With this functional material, we propose a tailorable and on-demand drug release with more control that can be employed for a combination drug therapy/single drug therapy combined with hyperthermia therapy for cancer cytotoxicity effect.

Water dispersible superparamagnetic Cobalt iron oxide nanoparticles for magnetic fluid hyperthermia

Superparamagnetic nanoparticles of Cobalt iron oxide (CoFe2O4) are synthesized chemically, and dispersed in an aqueous suspension for hyperthermia therapy application. Different parameters such as magnetic field intensity, particle concentration which regulates the competence of CoFe2O4 nanoparticle as a heating agents in hyperthermia are investigated. Specific absorption rate (SAR) decreases with increase in the particle concentration and increases with increase in applied magnetic field intensity. Highest value of SAR is found to be 91.84Wg−1 for 5mg. mL−1 concentration. Oleic acid conjugated polyethylene glycol (OA-PEG) coated CoFe2O4 nanoparticles have shown superior cyto-compatibility over uncoated nanoparticles to L929 mice fibroblast cell lines for concentrations below 2mg. mL−1. Present work provides the underpinning for the use of CoFe2O4 nanoparticles as a potential heating mediator for magnetic fluid hyperthermia.

Magnetic nanoparticles with high specific absorption rate of electromagnetic energy at low field strength for hyperthermia therapy.

Magnetic nanoparticles (MNPs), referred to as the Dartmouth MNPs, which exhibit high specific absorption rate at low applied field strength have been developed for hyperthermia therapy applications. The MNPs consist of small (2-5 nm) single crystals of gamma-Fe2O3 with saccharide chains implanted in their crystalline structure, forming 20-40 nm flower-like aggregates with a hydrodynamic diameter of 110-120 nm. The MNPs form stable (>12 months) colloidal solutions in water and exhibit no hysteresis under an applied quasistatic magnetic field, and produce a significant amount of heat at field strengths as low as 100 Oe at 99-164 kHz. The MNP heating mechanisms under an alternating magnetic field (AMF) are discussed and analyzed quantitatively based on (a) the calculated multi-scale MNP interactions obtained using a three dimensional numerical model called the method of auxiliary sources, (b) measured MNP frequency spectra, and (c) quantified MNP friction losses based on magneto-viscous theory. The frequency responses and hysteresis curves of the Dartmouth MNPs are measured and compared to the modeled data. The specific absorption rate of the particles is measured at various AMF strengths and frequencies, and compared to commercially available MNPs. The comparisons demonstrate the superior heating properties of the Dartmouth MNPs at low field strengths (<250 Oe). This may extend MNP hyperthermia therapy to deeper tumors that were previously non-viable targets, potentially enabling the treatment of some of the most difficult cancers, such as pancreatic and rectal cancers, without damaging normal tissue.

2A2-C06 金ナノ粒子を分散させたアルギン酸ゲル粒とそのハイパーサーミア応用

2A2-C06 金ナノ粒子を分散させたアルギン酸ゲル粒とそのハイパーサーミア応用

Particle size dependence of heating power in MgFe2O4 nanoparticles for hyperthermia therapy application

Magnetic nanoparticles with narrow size distributions have successfully been synthesized by an ultrasonic assisted co-precipitation method. The effects of particle size on magnetic properties, heat generation by AC fields, and the cell cytotoxicity were investigated for MgFe2O4 nanoparticles with mean diameters varying from 7 ± 0.5 nm to 29 ± 1 nm. The critical size for superparamagnetic to ferrimagnetic transition (DS→F) of MgFe2O4 was determined to be about 13 ± 0.5 nm at 300 K. The specific absorption rate (SAR) of MgFe2O4 nanoparticles was strongly size dependent; it showed a maximum value of 19 W/g when the particle size was 10 ± 0.5 nm at which the Néel and Brownian relaxations are the major cause of heating. The SAR value was suppressed dramatically by 46% with increasing particle size from 10 ± 0.5 nm to 13 ± 0.5 nm, where Néel relaxation slows down and SAR results primarily from Brownian relaxation loss. A further reduction in SAR value was evident when the size was increased from 13 ± 0.5 nm to 16 ± 1 nm, where the superparamagnetic to ferromagnetic transition occurs. However, SAR showed a tendency to increase with particle size again above 16 ± 1 nm where hysteresis loss becomes the dominant mechanism of heat generation. The particle size dependence of SAR in the superparamagnetic region was well described by considering the effective relaxation time estimated based on a log-normal size distribution. The clear size dependence of SAR is attributable to the high degree of monodispersity of particles synthesized here. The high SAR value of water-based MgFe2O4 magnetic suspension combined with low cell cytotoxicity suggests a great potential of MgFe2O4 nanoparticles for magnetic hyperthermia therapy applications.

Superparamagnetic iron oxide/chitosan core/shells for hyperthermia application: Improved colloidal stability and biocompatibility

Superparamagnetic magnetite nanoparticles are of great interest due to their potential biomedical applications. In the present investigation, Fe3O4 magnetic nanoparticles were prepared by alkaline precipitation using ferrous chloride as the sole source. An amphiphilic polyelectrolyte with the property of biocompatibility and functional carboxyl groups was used as a stabilizer to prepare a well-dispersed suspension of superparamagnetic Fe3O4 nanoparticles. The final material composed of Fe3O4 core and chitosan (CH) shell was produced. The amino groups of CH coated on Fe3O4 nanoparticles were further cross linked using glutaraldehyde (GLD) for stable coating. FTIR spectra, XPS and TGA confirmed the coating of CH/GLD on the surface of Fe3O4 nanoparticles. XRD patterns indicate the pure phase Fe3O4 with a spinel structure. The nanoparticles were superparamagnetic at room temperature with saturation magnetization values for bare and coated nanoparticles which were 51.68emu/g and 48.60emu/g, respectively. Zeta potential values showed higher colloidal stability of coated nanoparticles than the bare one. Cytotoxicity study up to 2mgmL−1 concentration showed no drastic change in cell viability of nanoparticles after coating. Also, coated nanoparticles showed increased SAR value, making them suitable for hyperthermia therapy application.

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.

New ${\rm T}_{\rm c}$-Tuned Manganese Ferrite-Based Magnetic Implant for Hyperthermia Therapy Application

The aim of this work is to develop a new low-Tc magnetic implant material with high heat generation and self-controlled capability for hyperthermia treatments based on a new class of Mn1+xTixFe2-2xO4 spinel ferrite. Magnetic Mn1+xTixFe2-2xO4 ferrites were successfully prepared by a coprecipitation technique. The structural and magnetic properties were characterized using X-ray diffraction (XRD), thermomagneto-gravimetric analysis (TMGA), and vibrating sample magnetometer (VSM). The heat generation ability of these magnetic materials was evaluated by calorimetric measurements of specific absorption rate (SAR). XRD results demonstrated an increase in the lattice constant of Mn-ferrites with increasing Ti content, whereas showed a tendency to decrease linearly with increasing Ti content in the Mn-ferrite. Tc was confirmed to be tunable within the therapeutic temperature range by adjusting the Ti4+ content near x = 0.55. These behaviors could be explained by considering the lattice expansion in the spinel structure of Mn-ferrites, which was accompanied by a decrease in the overlap of orbital and the JA-B superexchange interaction. The SAR value obtained was about 17.5 W/g with a maximum self-controlled temperature within the safe therapeutic range (42-46°C). MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay results confirmed that the toxicity of bare ferrite particles was related to the particle concentration. The cell viability showed a decrease from 93% to 66% with increasing particle concentration from 0.05 to 10 mg/ml. The high saturation magnetization and SAR of Mn1.55Ti0.55Fe0.9 along with tunability of its Curie temperature in the therapeutic temperature range, and its relatively low cytotoxicity rendered this new magnetic material attractive for hyperthermia therapy applications in comparison with other Tc-tuned spinel ferrites.

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.

Synthesis of well-dispersed layered double hydroxide core@ordered mesoporous silica shell nanostructure (LDH@mSiO2) and its application in drug delivery

We demonstrate an efficient synthesis of novel layered double hydroxide mesoporous silica core-shell nanostructures (LDH@mSiO(2)) that have a hexagonal MgAl-LDH nanoplate core and an ordered mesoporous silica shell with perpendicularly oriented channels via a surfactant-templating method. Transmission electron microscopy, X-ray diffraction and N(2) sorption analyses confirmed that the obtained nanostructures have uniform accessible mesopores (∼2.2 nm), high surface area (∼430 m(2) g(-1)), and large pore volume (∼0.22 cm(3) g(-1)). Investigations of drug release and bio-imaging showed that this material has a slow release effect of ibuprofen and good biocompatibility. This work provides an economical approach to fabricate LDH@mSiO(2) core-shell nanostructures, which may have great potential in broad drug delivery and hyperthermia therapy applications.

Measurement of Minute Changes in Magnetic Flux Density by Means of a Novel GMR Needle Probe for Application in Hyperthermia Therapy

The accuracy of heat deposition, which is proportional to magnetic fluid weight density, appears to be a major factor in the quality of magnetic-fluid-based hyperthermia. An innovative giant magnetoresistance (GMR) needle probe is proposed as a means of estimating very-low-concentration magnetic fluid weight density in a low-invasive way. The method of estimation is based on the difference between magnetic flux densities inside and outside a magnetic-fluid-filled area in the body, given that the applied magnetic flux density is uniform. Since, for very-low magnetic fluid weight densities the percentage change in magnetic flux density is in the order of 1/100, it is important that the applied magnetic flux density be at least 1/10th more uniform. For this purpose a Lee-Whiting type coil was designed and fabricated, producing a 0.001% fluctuation from the center of the coil in approximately 35% of the outer coil spacing along the axial direction and 25% of the diameter of the coils in the radial direction. Concentrations as low as 0.03% weight density (a change in magnetic flux density in the order of nanotesla) were estimated by means of a GMR needle probe.