Magnetic Hyperthermia Research Articles

Magnetite nanoparticles: an emerging adjunctive tool for the improvement of cancer immunotherapy.

Cancer immunotherapy has emerged as a groundbreaking field, offering promising and transformative tools for oncological research and treatment. However, it faces several limitations, including variations in cancer types, dependence on the tumor microenvironments (TMEs), immune cell exhaustion, and adverse reactions. Magnetic nanoparticles, particularly magnetite nanoparticles (MNPs), with established pharmacodynamics and pharmacokinetics for clinical use, hold great promise in this context and are now being explored for therapeutic aims. Numerous preclinical studies have illustrated their efficacy in enhancing immunotherapy through various strategies, such as modulating leukocyte functions, creating favorable TMEs for cytotoxic T lymphocytes, combining with monoclonal antibodies, and stimulating the immune response via magnetic hyperthermia (MHT) treatment (Front Immunol. 2021;12:701485. doi: 10.3389/fimmu.2021.701485). However, the current clinical trials of MNPs are mostly for diagnostic aims and as a tool for generating hyperthermia for tumor ablation. With concerns about the adverse effects of MNPs in the in vivo systems, clinical translation and clinical study of MNP-boosted immunotherapy remains limited. The lack of extensive clinical investigations poses a current barrier to patient application. Urgent efforts are needed to ascertain both the efficacy of MNP-enhanced immunotherapy and its safety profile in combination therapy. This article reviews the roles, potential, and challenges of using MNPs in advancing cancer immunotherapy. The application of MNPs in boosting immunotherapy, and its perspective role in research and development is also discussed.

Improvement of Phased Antenna Array Applied in Focused Microwave Breast Hyperthermia.

Focused microwave breast hyperthermia (FMBH) employs a phased antenna array to perform beamforming that can focus microwave energy at targeted breast tumors. Selective heating of the tumor endows the hyperthermia treatment with high accuracy and low side effects. The effect of FMBH is highly dependent on the applied phased antenna array. This work investigates the effect of polarizations of antenna elements on the microwave-focusing results by simulations. We explore two kinds of antenna arrays with the same number of elements using different digital realistic human breast phantoms. The first array has all the elements' polarization in the vertical plane of the breast, while the second array has half of the elements' polarization in the vertical plane and the other half in the transverse plane, i.e., cross polarization. In total, 96 sets of different simulations are performed, and the results show that the second array leads to a better focusing effect in dense breasts than the first array. This work is very meaningful for the potential improvement of the antenna array for FMBH, which is of great significance for the future clinical applications of FMBH. The antenna array with cross polarization can also be applied in microwave imaging and sensing for biomedical applications.

Synthesis and characterization of monophasic MnFe2O4 nanoparticles for potential application in magnetic hyperthermia

Nanostructured materials are being used in a wide range of technological applications. In biomedical applications, magnetic hyperthermia (MH) is a therapeutic modality for the treatment of solid tumors. The materials needed for MH face challenges such as size homogeneity, reasonable temperature increase and biocompatibility. In this work, MnFe2O4 magnetic nanoparticles (Nps) were synthesized by a simple method using the bio-polymer chitosan. Samples with several particles sizes were obtained by treatments at the temperatures of 300, 400, 500 and 600 °C. The particle sizes ranged from 7.8 to 13.3 nm. At 300 K, the saturation magnetization of the Nps varied from 16.2 to 35.8 emu/g. The Mössbauer spectra at low temperatures showed the presence of monophasic MnFe2O4. For all samples, the Mössbauer results at 300 K suggest that the samples are in the superparamagnetic regime. The measurements to obtain the Specific Loss Power (SLP) were conducted at a frequency of 74 kHz and AC field amplitude of 247 Oe. The sample thermally treated at 600 °C and the dispersion prepared with a concentration of 1.0 mg/mL showed the highest SLP of 129.1 W/g.

Controlled Release of the Anticancer Drug Cyclophosphamide from a Superparamagnetic β-Cyclodextrin Nanosponge by Local Hyperthermia Generated by an Alternating Magnetic Field.

A β-cyclodextrin (β-CD) nanosponge (NS) was synthesized using diphenyl carbonate (DPC) as a cross-linker to encapsulate the antitumor drug cyclophosphamide (CYC), thus obtaining the NSs-CYC system. The formulation was then associated with magnetite nanoparticles (MNPs) to develop the MNPs-NSs-CYC ternary system. The formulations mentioned above were characterized to confirm the deposition of the MNPs onto the organic matrix and that the superparamagnetic nature of the MNPs was preserved upon association. The association of the MNPs with the NSs-drug complex was confirmed through field emission scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, ζ-potential, atomic absorption spectroscopy, X-ray powder diffraction, selected area electron diffraction, and vibrating-sample magnetometer. The superparamagnetic properties of the ternary system allowed the release of CYC by utilizing magnetic hyperthermia upon the exposure of an alternating magnetic field (AMF). The drug release experiments were carried out at different frequencies and intensities of the magnetic field, complying with the "Atkinson-Brezovich criterion". The assays in AMF showed the feasibility of release by controlling hyperthermia of the drug, finding that the most efficient conditions were F = 280 kHz, H = 15 mT, and a concentration of MNPs of 5 mg/mL. CYC release was temperature-dependent, facilitated by local heat generation through magnetic hyperthermia. This phenomenon was confirmed by DFT calculations. Furthermore, the ternary systems outperformed the formulations without MNPs regarding the amount of released drug. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays demonstrated that including CYC within the magnetic NS cavities reduced the effects on mitochondrial activity compared to those observed with the free drug. Finally, the magnetic hyperthermia assays showed that the tertiary system allows the generation of apoptosis in HeLa cells, demonstrating that the MNPs embedded maintain their properties to generate hyperthermia. These results suggest that using NSs associated with MNPs could be a potential tool for a controlled drug delivery in tumor therapy since the materials are efficient and potentially nontoxic.

Minimally Invasive Delivery of Percutaneous Ablation Agent via Magnetic Colloidal Hydrogel Injection for Treatment of Hepatocellular Carcinoma.

Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.

Exploring BiFeO3/Fe3O4 nanocomposite for possible application in magnetic hyperthermia

The development of perovskite/spinel nanocomposite BiFeO3/Fe3O4 (BFO/FO) holds particular interest for applications in magnetic hyperthermia therapy (MHT). This work offers a significant avenue for advancing material properties and evaluating the heating efficiency, considering the impact of structure, and magnetic characteristics within the perovskite/spinel system. A sol–gel synthesis process for phase-pure BiFeO3 production was successful, which is subsequently utilized with Fe3O4 to form a nanocomposite (BiFeO3)1−x/(Fe3O4)x. Our findings indicate that increasing the concentration of Fe3O4 in the nanocomposite enhances the saturation magnetization and the specific absorption rate (SAR). Importantly, the addition of BiFeO3 to Fe3O4 further enhances the nanocomposite's heating efficiency. This study underscores the potential of perovskite/spinel nanocomposites in realizing advanced materials with tailored properties and multifaceted functionalities.

Hydrazine metal complexes as a single source in the mechanochemical preparation of metallic magnetic nanoparticles and investigation of their magnetic hyperthermia properties

Ferromagnetic metallic cobalt and nickel nanoparticles were synthesized by intramolecular metal-hydrazine ligand oxidation reduction reaction in basic media and the solid state. Nickel nanoparticles Ni1 and Ni2 are obtained from two complexes, Ni(N2H4)2(C2O4) and Ni(N2H4)2(HCO2)2, respectively. X-ray powder diffraction (XRD) and energy-dispersive X-ray (EDX) data show pure fcc crystal structures of nanoparticles. Scanning electron microscopy (SEM) images revealed both Ni1 and Ni2 nanoparticles have agglomerated sphere morphologies. The crystallite size estimated by using the Scherer method for Ni1 and Ni2 were 18.7 and 6.2 nm. Vibrating sample magnetometer (VSM) data show the coercivity of metallic nickel samples Ni1 and Ni2 are 50 and 153 Oe, respectively. Both nanoparticles cause an increase in the temperature of water under applied alternative magnetic field and showed specific loss power (SLP) of 70 W/g and 104.8 W/g, respectively. The same method is used in preparation of cobalt nanoparticles from two complexes, Co(N2H4)2(C2O4) and Co(N2H4)2(HCO2)2. XRD analysis data show both nanoparticles have hcp crystal structure. SEM images show nanosheet structure with sheet thickness of 10 to 30 nm. Coercivity of Co1 and Co2 nanoparticles obtained by VSM and Hc are 182 and 171 Oe, respectively. In spite of high coercivity in both Co1 and Co2 nanoparticles, the magnetic hyperthermia heating effects are not observed in practice and specific loss power (SLP) is zero.

Application of Nanotechnology in Organ Transplantation

Organ transplantation can serve as a blessing for end-stage organ patients, and issues such as organ shortage and transplantation risks also make research on organ transplantation very important. Nanotechnology involves the development of materials called nanoparticles, which are defined as having a one-dimensional range of at least 1 to 100 nm. This paper introduces the application of nanotechnology in overcoming the drawbacks of traditional medicine, and its nanoscale size has also contributed to organ transplantation. The combination of Magnetic resonance imaging (MRI) and Magnetic hyperthermia (MHT), nanoparticles can better capture transplant medical images, and nanotechnology plays an important role in monitoring treatment responses and designing organ transplantation methods. CRISPR/CAS9 system and Entrancer™ can reduce the role in rejection reactions. Normothermic Machine Perfusion (NMP), protein corona, and curcumin can reduce their effects on ischemia-reperfusion injury. The development of nanomedicine can provide a platform for significant progress in transplant vitality. In future research, nanoparticles can also be applied in 3D bioprinting and artificial intelligence (AI) to better assist in transplant therapy.

Induction heating of magnetic nanoparticles: role of thermo-physical properties of the coating moieties

Superparamagnetic nanoparticles (MNPs) are utilized for magnetic fluid hyperthermia (MFH)-based cancer therapeutics, where the MNPs are surface functionalized to impart desired stability and biological properties. In this study, the MFH properties of palmitic (PA) and stearic (SA) acid-coated superparamagnetic Fe3O4 MNPs, with similar sizes (∼ 10 ± 0.8 nm, and ∼ 11 ± 0.7 nm, respectively), and saturation magnetizations (∼ 40.8 emu/g, and ∼ 41 emu/g, respectively), are systematically probed to understand the role of the thermo-physical properties of the coating moieties on the MFH efficiency. PA and SA-coated MNPs are prepared using a one-step microwave-assisted co-precipitation technique, and the presence of the surface coatings is confirmed using Fourier transform infrared spectroscopy and thermogravimetric analyses. Magneto-calorimetric studies show a high induction heating efficiency, surpassing the threshold of MFH for a biologically relevant field-frequency range. The maximum heating efficiencies are found to be ∼ 164.5 ± 5.4 W/gFe and ∼ 223.9 ± 6.4 W/gFe for the PA and SA-coated MNPs, respectively. This indicates ∼ 36.1 % higher specific absorption rate (SAR) for the SA-coated MNPs under similar experimental conditions, even though the magneto-structural properties are identical for the PA and SA-coated MNPs. Further, finite element modelling is utilized to investigate the thermal transport from the magnetic core to the surrounding medium, where the thermo-physical properties of the coating moieties are considered. Finite element simulations indicate ∼ 32.6 % higher SAR for the SA-coated MNPs, which is consistent with the experimental findings. The higher SAR for the SA-coated MNPs is attributed to the ∼ 1.7 times higher thermal diffusivity of SA. The proposed model is experimentally validated using a third system consisting of lauric acid-coated Fe3O4 MNPs with comparable magneto-structural properties. Further, significant temperature rise in a tissue-equivalent agar medium and good bio-compatibility, as indicated by the in vitro cyto-toxicity studies, make the prepared MNPs potential candidates for MFH applications. The obtained results provide deeper insight into the role of the thermo-physical properties of the coating moieties on the induction heating efficiency of superparamagnetic MNPs.

Magnetic hyperthermia in cancer therapy, mechanisms, and recent advances: A review.

Hyperthermia therapy refers to the elevating of a region in the body for therapeutic purposes. Different techniques have been applied for hyperthermia therapy including laser, microwave, radiofrequency, ultrasonic, and magnetic nanoparticles and the latter have received great attention in recent years. Magnetic hyperthermia in cancer therapy aims to increase the temperature of the body tissue by locally delivering heat from the magnetic nanoparticles to cancer cells with the aid of an external alternating magnetic field to kill the cancerous cells or prevent their further growth. This review introduces magnetic hyperthermia with magnetic nanoparticles. It includes the mechanism of the operation and magnetism behind the magnetic hyperthermia phenomenon. Different synthesis methods and surface modification to enhance the biocompatibility, water solubility, and stability of the nanoparticles in physiological environments have been discussed. Recent research on versatile types of magnetic nanoparticles with their ability to increase the local temperature has been addressed.

Development of polymeric nanoparticles associated with SPION and curcumin: a versatile magnetic and fluorescent platform for Life Science applications

Magnetic nanoparticles are prominent in biomedical applications due to their adjustable properties through surface functionalization and inherent magnetism. In the present manuscript, multifunctional nanoparticles were synthesized by combining polymer with a fluorophore and magnetic nanoparticles, resulting in a magnetic and fluorescent nanomaterial. A miniemulsion polymerization technique was employed, using the comonomers methyl methacrylate (MMA) and acrylic acid (AA) in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) and natural turmeric extract (curcumin). Physicochemical characterizations revealed efficient encapsulation of SPIONs within the polymer matrices while maintaining superparamagnetic behavior. The nanosystems exhibited ILP values consistent with those commonly used for magnetic hyperthermia applications, ranging from 0.13 – 0.32 nHm2 kg−1. Additionally, a high fluorescence intensity in the blue/green region was observed, alongside no cell toxicity and substantial internalization in human osteosarcoma cells (OSAS2). Given their intrinsic magnetic and fluorescent properties exhibited, the nanosystems can be considered potential candidates for cell tracking and as a platform in nanotheranostics (MRI, magnetic hyperthermia, and photodynamic therapy).

Magnetic hybrid nanomaterial based on a natural polymer and an amino acid as pH/temperature dual-responsive nanoplatform for the delivery of tamoxifen

Magnetic hybrid nanomaterials offer promising properties for the advancement of nanoplatforms in cancer nanomedicine, particularly in drug delivery applications. These nanoplatforms can effectively respond to various stimuli present at the tumor site, such as pH and temperature fluctuations, allowing for controlled and triggered release of therapeutic payloads. In this study, we present a straightforward methodology for the synthesis of stable hybrid magnetic nanoplatforms (HMNP) based on Fe3O4 nanoparticles, L-cysteine (L-Cys), and hyaluronic acid (HA) as key constituents for the delivery of tamoxifen (TMX). The synthesized superparamagnetic HMNP, Fe3O4-L-Cys-HA, with a size of 11 nm, was successfully loaded with TMX. The incorporation of L-Cys showed superior interaction with the surface of Fe3O4 nanoparticles compared to other L-Cys derivatives explored as ligands. Consequently, L-Cys was selected for further functionalization with HA, providing the HMNP with active targeting properties toward CD44-overexpressed receptors. High loading efficiency of TMX (75%) was achieved via electrostatic interaction between the carboxylate groups exposed by the HMNP and the ammonium group of the TMX side chain. Efficient control in the TMX release towards different receptor media was observed. Notably, the release of TMX from HMNP-TMX was triggered under acidic pH and hyperthermia conditions, showcasing its responsiveness to both stimuli. Furthermore, enhanced anticancer activity of TMX against MDA-MB-231 breast cancer cells was observed when loaded into HMNP (IC50 almost 3-fold lower for HMNP-TMX compared to free TMX), indicating improved cell uptake of TMX-loaded HMNP in comparison to the free drug. Overall, pH/temperature dual-sensitive HMNP demonstrates promising potential as a nanoplatform for cancer nanomedicine, with prospects for magnetic hyperthermia therapy.

Magnetic membranes based on PVA-SPION for hyperthermia and dielectric applications

Magnetodielectric membranes were spun by electrospinning ferrofluids containing Superparamagnetic Iron Oxide (SPION) in a carrier liquid of Polyvinyl alcohol(PVA) for various loadings of iron oxide. These membranes were characterised using X-ray diffractometer (XRD), Field Emission Scanning Electron Microscopy (FESEM),Vibrational Sample Magnetometry (VSM),Fourier Transform Infrared Spectroscopy (FTIR) and UV–visible spectroscopy (UV–vis) and found to be of good quality having adequate magnetic and dielectric properties. The iron oxide particles were found to be ∼9 nm in size and superparamagnetic in nature. The addition of iron oxide led to a systematic increase in both magnetic and dielectric properties. A maximum saturation magnetization of ∼6.3 emu g−1 and a dielectric constant of ∼50 was obtained for a loading of 40 percentage of Iron oxide. A dielectric transducer was fabricated using the membranes. These membranes also exhibited magnetic hyperthermia as evidenced by magnetic hyperthermia measurements. They are found to be potential candidates for hyperthermia applications as wearables. The method of employing a ferrofluid can be adopted for spinning membranes based on other than PVA/SPION. If the loading is optimised these membranes can be employed as Magnetodielectric transducers.

Iron Oxide Nanoparticles: Selectively Targeting Melanoma Cells In Vitro by Inducing DNA Damage via H2AX Phosphorylation and Hindering Proliferation through ERK Dephosphorylation.

This study investigates the distinctive characteristics of iron oxide magnetic nanoparticles (mNPs) and their potential application in cancer therapy, focusing on melanoma. Three types of mNPs, pre-validated for safety, underwent molecular analysis to uncover the activated signaling pathways in melanoma cells. Using the Western blot technique, the study revealed that mNPs induce cytotoxicity, hinder proliferation through ERK1/2 dephosphorylation, and prompt proapoptotic effects, including DNA damage by inducing H2AX phosphorylation. Additionally, in vitro magnetic hyperthermia notably enhanced cellular damage in melanoma cells. Moreover, the quantification of intracellular iron levels through Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis unveils the precise dosage required to induce cellular damage effectively. These compelling findings not only shed light on the therapeutic potential of mNPs in melanoma treatment but also open exciting avenues for future research, heralding a new era in the development of targeted and effective cancer therapies. Indeed, by discerning the effective dose, our approach becomes instrumental in optimizing the therapeutic utilization of iron oxide magnetic nanoparticles, enabling the induction of precisely targeted and controlled cellular responses.

The Latest Studies for the Manufacture of Nanoparticles in Iraq during the Last Ten Years Ago

Silver nanoparticles (AgNPs) have gained immense consideration recently as a result of their exceptional properties and diverse interference in a variety of fields. The AgNPs synthesis involves various and biological, chemical, and physical methods, each offering distinct compensations in terms of size control, stability, and reproducibility. Physical methods, such as irradiation, result in monodisperse nanoparticles with excellent control over size and shape. Chemical techniques, like reduction with reducing agents or chemical precursors, offer scalability and control over nanoparticle size. Moreover, green synthesis methods employing plant extracts, fungi, and bacteria have emerged as eco-friendly alternatives, reducing the reliance on hazardous chemicals. Characterization of AgNPs is necessary to understand their characteristics and potential applications fully. Techniques such as X-ray diffraction (XRD), UV-Vis spectroscopy, light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM), dynamic are commonly used to identified anf characterized the nanoparticles. The applications of AgNPs span across several sectors. In the biomedical field, AgNPs exhibit potent antimicrobial properties against a broad spectrum of pathogens, making them promising candidates for wound dressings, antibacterial coatings, and drug delivery systems. Additionally, their use in cancer therapy has shown potential for targeted drug delivery and localized hyperthermia treatment. However, despite their numerous applications, challenges remain in terms of toxicity and environmental impact. Research efforts are ongoing to address these concerns and develop safer nanomaterials. This review article concludes that silver nanoparticles represent a fascinating class of nanomaterials with immense potential in various fields. Continued research and development in the synthesis, characterization, and application of AgNPs will undoubtedly lead to new and exciting advancements in science and technology.

Remote Control of Energy Transformation-Based Cancer Imaging and Therapy.

Cancer treatment requires precise tumor-specific targeting at specific sites that allows for high-resolution diagnostic imaging and long-term patient-tailorable cancer therapy; while, minimizing side effects largely arising from non-targetability. This can be realized by harnessing exogenous remote stimuli, such as tissue-penetrative ultrasound, magnetic field, light, and radiation, that enable local activation for cancer imaging and therapy in deep tumors. A myriad of nanomedicines can be efficiently activated when the energy of such remote stimuli can be transformed into another type of energy. This review discusses the remote control of energy transformation for targetable, efficient, and long-term cancer imaging and therapy. Such ultrasonic, magnetic, photonic, radiative, and radioactive energy can be transformed into mechanical, thermal, chemical, and radiative energy to enable a variety of cancer imaging and treatment modalities. The current review article describes multimodal energy transformation where a serial cascade or multiple types of energy transformation occur. This review includes not only mechanical, chemical, hyperthermia, and radiation therapy but also emerging thermoelectric, pyroelectric, and piezoelectric therapies for cancer treatment. It also illustrates ultrasound, magnetic resonance, fluorescence, computed tomography, photoluminescence, and photoacoustic imaging-guided cancer therapies. It highlights afterglow imaging that can eliminate autofluorescence for sustained signal emission after the excitation.

Magnetic Hyperthermia to Promote Acrylamide Radical Polymerizations

Magnetic Hyperthermia to Promote Acrylamide Radical Polymerizations

Eco-friendly synthesis of fluorescent cobalt-doped manganese ferrites for thermo-therapeutic applications

The synthesis of high-quality nanoparticles for biomedical applications through environmentally friendly methods is a major challenging task. In this work, oxidative precipitation and a novel method, oxidative hydrothermal synthesis, are explored as one-pot eco-friendly synthesis routes to obtain single phase multicore-like and single-core citrate-stabilized cobalt and/or manganese-doped ferrite (CoxMn1-xFe2O4, 0 ≤ x ≤ 1) nanoparticles, respectively. The Co2+/Mn2+ ratio and synthesis method were found to influence the nanoparticles' morphology and structure, with oxidative precipitation producing multicore-like structures and hydrothermal synthesis yielding single-core particles with crystalline sizes in the range of 2 − 10 nm and 4 − 11 nm, respectively. Inductively coupled plasma optical emission spectrometry (ICP-OES) indicated a composition near the expected values. Mixed ferrites displayed improved saturation magnetization up to 60 A.m2/kg, exhibiting superparamagnetism at room temperature. The particles’ stability was evaluated in physiological pH, and the mixed ferrites displayed intrinsic fluorescence emission in the violet-green range with a maximum wavelength near 425 nm. The cobalt and/or manganese-doped ferrites were evaluated for magnetic hyperthermia and photothermia, displaying high heating efficiency for several alternating magnetic field conditions (up to ∼2.5 nHm2/kg) compatible with biological applications, and high light-to-heat conversion efficiency (up to ∼53%) with near infrared (NIR) laser irradiation at 808 nm. Hereby, the oxidative precipitation and oxidative hydrothermal synthesis are promising eco-friendly methods for the development of crystalline citrate-stabilized cobalt and/or manganese-doped ferrites with multicore-like and single-core spherical morphology, respectively, without requiring additional post-synthesis treatments and with suitable properties for biomedical applications, such as magnetic hyperthermia, photothermia and as prospective fluorescent probes for bio-imaging.

Deregulated JNK signaling enhances apoptosis during hyperthermia

Purpose c-Jun N-terminal kinases (JNKs) comprise a subfamily of mitogen-activated protein kinases (MAPKs). The JNK group is known to be activated by a variety of stimuli. However, the molecular mechanism underlying heat-induced JNK activation is largely unknown. The aim of this study was to clarify how JNK activity is stimulated by heat. Methods and materials The expression levels of various MAPK members in HeLa cells, with or without hyperthermia treatment, were evaluated via western blotting. The kinase activity of MAPK members was assessed through in vitro kinase assays. Cell death was assessed in the absence or presence of siRNAs targeting MAPK-related members. Results Hyperthermia decreased the levels of MAP3Ks, such as ASK1 and MLK3 which are JNK kinase kinase members, but not those of the downstream MAP2K/SEK1 and MAPK/JNK. Despite the reduced or transient phosphorylation of ASK1, MLK3, or SEK1, downstream JNK was phosphorylated in a temperature-dependent manner. In vitro kinase assays demonstrated that heat did not directly stimulate SEK1 or JNK. However, the expression levels of DUSP16, a JNK phosphatase, were decreased upon hyperthermia treatment. DUSP16 knockdown enhanced the heat-induced activation of ASK1–SEK1–JNK pathway and apoptosis. Conclusion JNK was activated in a temperature-dependent manner despite reduced or transient phosphorylation of the upstream MAP3K and MAP2K. Hyperthermia-induced degradation of DUSP16 may induce activation of the ASK1–SEK1–JNK pathway and subsequent apoptosis.

Design and Modelling of an Induction Heating Coil to Investigate the Thermal Response of Magnetic Nanoparticles for Hyperthermia Applications

Magnetic Field Hyperthermia is a technique where tumours are treated through an increase in local temperature upon exposure to alternating magnetic fields (AMFs) that are mediated by magnetic nano-particles (MNPs). In an AMF, these particles heat-up and kill the cells. The relationship between an AMF and the heating-rate is complex, leading to confusion when comparing data for different MNP and AMF conditions. This work allows for the thermal-response to be monitored at multiple AMF amplitudes while keeping other parameters constant. An induction-heating coil was designed based on a Zero-Voltage-Zero-Current (ZVZC) resonant circuit. The coil operates at 93 kHz with a variable DC drive-voltage (12–30 V). NEC4 software was used to model the magnetic field distribution, and MNPs were synthesised by the coprecipitation method. The magnetic field was found to be uniform at the centre of the coil and ranged from 1 kAm−1 to 12 kAm−1, depending on the DC drive-voltage. The MNPs were found to have a specific absorption rate (SAR) of 1.37 Wg−1[Fe] and 6.13 Wg−1[Fe] at 93 kHz and 2.1 kAm−1 and 12.6 kAm−1, respectively. The measured SAR value was found to be directly proportional to the product of the frequency and field-strength (SARα f Ho). This leads to the recommendation that, when comparing data from various groups, the SAR value should be normalized following this relationship and not using the more common relationship based on the square of the field intensity (SARα f Ho2).