Magnetic Hyperthermia Research Articles

Improvement of the magnetization and heating ability of CoFe2O4/ NiFe2O4 core/shell nanostructures

Abstract In this study, the effect of the shell thickness on the structural and magnetic properties of the CoFe2O4/NiFe2O4 core/shell is studied. A single-phase core/shell nanocomposite was prepared by the hydrothermal method. The shell thickness was found to control the magnitudes of saturation magnetization and coercive field of the prepared samples. The thickness of the NiFe2O4, which covered cubic CoFe2O4 particles of 15 nm, was 1.8 nm, leading to an increase in the saturation magnetization by 26% and a decrease in the coercive field by 50% compared to bare CoFe2O4. However, a further increase in shell thickness caused interfacial dislocations due to the lattice mismatch between the core and the shell. Finally, the heating ability at high frequency was measured for all samples. Comparing the temperature rise under the influence of AC magnetic field, which indicates power loss, relative to bare CoFe2O4, it was enhanced by 100% for a shell thickness of 26 nm. The results of this study point to potential applications for these samples in the field of magnetic hyperthermia for cancer therapy and drug delivery.

Nebulized Immunotherapy of Orthotopic Lung Cancer by Mild Magnetothermal–Based Innate Immunity Activations

AbstractAdvances in adaptive immunity have greatly contributed to the development of cancer immunotherapy. However, its over‐low efficacy and insufficient invasion of immune cells in the tumor tissue, and safety problems caused by cytokine storm, have seriously impeded further clinical application for solid tumor immunotherapy. Notably, the immune microenvironment of the lungs is naturally enriched with alveolar macrophages (AMs). Herein, we introduce a novel nebulized magnetothermal immunotherapy strategy to treat orthotopic lung cancer by using magnetothermal nanomaterial (Zn−CoFe2O4@Zn−MnFe2O4−PEG, named ZCMP), which can release iron ions via an acid/thermal‐catalytic reaction to maximize the use of lung‘s immune environment through the cascade activations of AMs and natural killer (NK) cells. Nebulized administration greatly enhance drug bioavailability by localized drug accumulation at the lesion site. Upon mild magnetic hyperthermia, the released iron ions catalyze endogenous H2O2 decomposition to produce reactive oxygen species (ROS), which triggers the M1 polarization of AMs, and the resultant inflammatory cytokine IFN‐β, IL‐1β and IL‐15 releases to activate c‐Jun, STAT5 and GZMB related signaling pathways, promoting NK cells proliferation and activation. This innovative strategy optimally utilizes the lung‘s immune environment and shows excellent immunotherapeutic outcomes against orthotopic lung cancer.

Hyperthermia reduces cancer cell invasion and combats chemoresistance and immune evasion in human bladder cancer.

Bladder cancer (BC) is a common malignancy and its most prevalent type is urothelial carcinoma, which accounts for ~90% of all cases of BC. The current treatment options for BC are limited, which necessitates the development of alternative treatment strategies. Hyperthermia (HT), as an adjuvant cancer therapy, is known to improve the efficacy of chemotherapy or radiotherapy. The present study aimed to investigate the anti‑tumor effects of HT on cell survival, invasiveness, chemoresistance and immune evasion in human BC cell lines (5637, T24 and UMUC3). Calcein AM staining was performed to analyze the cytotoxicity of natural killer (NK) cells against human BC cells following HT treatment. Cell migration and invasion affected by HT were analyzed using Transwell migration and invasion assays. It was found that HT inhibited the proliferation of BC cells by downregulating the phosphorylation of protein kinase B. Moreover, HT effectively enhanced the sensitivity of BC cells to the chemotherapy drug cisplatin (DDP) and reduced the chemoresistance of DDP‑resistant cells by downregulating the expression of cadherin‑11. It was further demonstrated that HT inhibited the migration and invasion of BC cells and enhanced the cytotoxic effects of NK cells. In summary, the antineoplastic effects of HT were mediated through three main mechanisms: Enhancement of the chemosensitivity of BC cells and mitigation of DDP‑induced chemoresistance, suppression of the invasive potential of BC cells and reinforcement of the anticancer response of NK cells. Thus, HT appears to be a promising adjunctive therapy for human BC.

Cerium doped superparamagnetic Mn-Zn ferrite as a promising material for self-regulated magnetic hyperthermia

Recently, cubic ferrites (CF) have been widely explored in biomedical applications, especially those that display superparamagnetism behavior due to the desirable absence of remanent field. In this study, we report the self-stabilization of the magnetic fluid hyperthermia (MFH) temperature in the cancer therapy range (42 - 48 ºC) by Ce3+ substitution in superparamagnetic Mn0.8Zn0.2Fe2-xCexO4 ferrite with x = 0.0; 0.015; 0.030; 0.050 and 0.100. A comprehensive characterization was performed in order to investigate the influence of this replacement on the magnetic and structural properties of the ferrite. The samples were synthesized by the sol-gel auto-combustion method and the properties were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), Raman spectroscopy (RS), Mössbauer spectroscopy (MS), vibrational sample magnetometry (VSM), and ferromagnetic resonance (FMR). Magnetic hyperthermia essays were used to obtain the heat induction curves and calculate energy dissipation. We refined the XRD data by the Rietveld method to determine the cation distribution and calculate interionic parameters. Magnetic characterization confirms the superparamagnetic behavior at 300 K, which is expected from the TEM results that show a narrow distribution of particle sizes, with a mean size of about 6.5 nm for all samples. The VSM results show a consistent decrease in magnetization saturation with cerium content that result in a weaker self-heating induction capacity for the cerium-doped samples. FMR results also show a smaller relaxation time T2 for these samples, suggesting a slower energy dissipation rate. These conclusions are confirmed by the heat induction curves and the values of the specific absorption rate (SAR), which are smaller for cerium-doped samples. For the a field with an amplitude of 35.33 kA/m and a frequency of 222 kHz, the temperature of the cerium-doped samples saturates in the optimum interval for cancer treatment, between 42 and 48 ºC. These results suggest that Ce3+ is a promising doping ion to optimize the heating rate behavior of Mn-Zn ferrite for cancer treatment by hyperthermia.

Thermal Wave and Pennes’ Models of Bioheat Transfer in Human Skin: A Transient Comparative Analysis

The primary focus of this study is to analyze comparative heat transfer in a two-dimensional (2D) multilayered human skin using thermal waves and Pennes' bioheat transfer models. The model comprises the epidermis, dermis, hypodermis tissue, and inner cells, and aims to understand their response to microwave (MW) power and electromagnetic (EM) frequency. The system of equations involves EM wave frequency and bioheat equations and uses the finite element method (FEM) for solving. It encompasses a range of microwave power levels (4-16 W), frequencies (0.9-4 GHz), and exposure durations (0-180 s). It examines how MW power and frequency affect temperature predictions due to different relaxation times. The results are visually represented, illustrating microwave power dissipation, isothermal profiles within the skin tissue, temperature trends at several locations, relaxation times, specific absorption rate (SAR), and the mean surface temperature of the multilayered dermal cell. Thermal analysis shows that Pennes' equation predicts higher temperatures than the thermal wave model of bioheat transfer (TWMBT). A notable disparity in temperature evolution is observed between the two models, especially in high-frequency transient heating scenarios. The TWMBT forecasts a delay in heat transfer, offering valuable insights into the more realistic short-term thermal behavior that the classical Pennes' model fails to capture. This comparative study underscores the significance of selecting an appropriate bioheat transfer model for precise thermal analysis in biomedical applications, such as hyperthermia treatment and thermal diagnostics. The findings emphasize the potential of the TWMBT to enhance the accuracy of thermal treatments in clinical settings.

Synergetic effect of Hexaferrite and reduced Graphene oxide (rGO) in Photothermal therapy and Hyperthermia applications

This research article describes the synthesis of composite materials by combining T-type hexagonal ferrite and reduced Graphene Oxide using the standard ceramic process. The Calcium-based T-type hexagonal ferrite was synthesized by using the sol-gel auto-combustion method whiles the reduced graphene oxide by adopting the Hummer method. The crystallite size varied in the range of 34.11 to 42.07nm as calculated from the X-ray diffraction (XRD) data. Consequently, the lattice parameters 'a' and 'c' decreased from 5.9 to 5.1Å and from 29.92 to 28.32Å, respectively. The use of atomic force microscopy (AFM) revealed a range of particle sizes at the surface, varying from 1.70nm to 3.85nm. Moreover, the saturation and remanence magnetization values demonstrated an increasing trend with T-type hexaferrites concentration whereas the coercivity decreased. The UV-vis near-infrared spectra exhibited substantial light absorption, characterized by a wide absorption range in the visible and near-infrared (NIR) region (700 to 1100nm) which indicates its use in Photothermal therapy (PTT). The Calcium T- type hexaferrite exhibited clear peaks in the blue, green, violet, and yellow spectra in its photoluminescence (PL) properties. These peaks are believed to be caused by oxygen vacancies and defects. The synthesized samples displayed a lossy behavior in the polarization-electric field (P-E) loop, with saturation polarization levels exceeding remnant polarization, which is an amenable condition for lossy behavior. Most importantly, the synthesized materials had significant thermal responses when exposed to an alternation (AC) magnetic field, indicating their potential use in magnetic hyperthermia applications.

Modulating Drug Retention and Release via Surface Anchors Using Hyperthermia and Photothermal Effects of Fe3O4-SiO2 Core-shell Mesoporous Nanoparticles

Core-shell nanocarriers (Fe3O4-MSN-TESPA-PEG/DOX) with a core-shell structure were created as possible materials for controlled drug retention and release. With a notable increase in pore volume and surface area, the 3-(Trimethylsilyl)propionic acid (TESPA) anchors on the pore walls of SiO2 nanoparticles (MSN). The doxorubicin (DOX) is controlled and stored by a network of polyethylene glycol (PEG) layers that cover the MSN pore by TESPA anchor as a result of interactions between the layers and the high density of functional groups at the pore mouth. Rather than the Brownian motion contribution, magnetic hysteresis losses account for the magnetic hyperthermia contribution to the heating efficiency of the investigated core-shell configuration. Fe3O4 NPs' magnetism and capacity for photothermal conversion make its core an appealing choice for photothermal treatment. By appropriately adjusting the following variables, the combination of magnetic field and NIR irradiation can control localized heating: i. NIR irradiation density; ii. magnetic field intensity; iii. time of use; and iv. concentration of Fe3O4-MSN-TESPA-PEG/DOX core-shell solution. This combination is ideal for bioapplications and clinical trials. The two-step NIR irradiation procedure or magnetic field intensity control allows for the rapid delivery of roughly seven times the maximum amount of stored doxorubicin in only five minutes. Fe3O4-MSN-TESPA-PEG nanocarriers with their core-shell structure have great potential as therapeutic agents with controllable drug delivery and targetability.

Metal Nanoparticles for Simultaneous Use in AC Magnetic Field Hyperthermia and Magnetic Resonance Imaging.

Magnetic nanoparticles (MNPs) are produced for both diagnosis and treatment due to their simultaneous availability in magnetic resonance imaging (MRI) and magnetic hyperthermia (MHT). Extensive investigations focus on developing MNPs for individual MHT or MRI applications, but the development of MNPs for theragnostic applications has received very little attention. In this study, through efficient examination of synthesis conditions such as metal precursors, reaction parameters, and solvent choices, we aimed to optimize MNP production for effective utilization for MHT and MRI simultaneously. MNPs were synthesized by thermal decomposition under 17 different conditions and deeply characterized by transmission electron microscopy (TEM), x-ray diffraction (XRD), and x-ray photoelectron spectroscopy (XPS). The heating efficiency of MNPs under an alternating current (AC) magnetic field was quantified, while MRI performance was evaluated through agar phantom experiments. Our findings highlight the crucial role of benzyl ether in metal ion reduction and size control. Metal-doped iron oxide MNPs displayed promise for MHT, whereas Mn-doped iron oxide MNPs exhibited enhanced MRI capabilities. Consequently, five engineered MNPs were considered potential candidates for further studies, demonstrating their dual ability in MRI and MHT.

Targeting the undruggable in glioblastoma using nano-based intracellular drug delivery.

Glioblastoma (GBM) is a highly prevalent and aggressive brain tumor in adults with limited treatment response, leading to a 5-year survival rate of less than 5%. Standard therapies, including surgery, radiation, and chemotherapy, often fall short due to the tumor's location, hypoxic conditions, and the challenge of complete removal. Moreover, brain metastases from cancers such as breast and melanoma carry similarly poor prognoses. Recent advancements in nanomedicine offer promising solutions for targeted GBM therapies, with nanoparticles (NPs) capable of delivering chemotherapy drugs or radiation sensitizers across the blood-brain barrier (BBB) to specific tumor sites. Leveraging the enhanced permeability and retention effect, NPs can preferentially accumulate in tumor tissues, where compromised BBB regions enhance delivery efficiency. By modifying NP characteristics such as size, shape, and surface charge, researchers have improved circulation times and cellular uptake, enhancing therapeutic efficacy. Recent studies show that combining photothermal therapy with magnetic hyperthermia using AuNPs and magnetic NPs induces ROS-dependent apoptosis and immunogenic cell death providing dual-targeted, immune-activating approaches. This review discusses the latest NP-based drug delivery strategies, including gene therapy, receptor-mediated transport, and multi-modal approaches like photothermal-magnetic hyperthermia combinations, all aimed at optimizing therapeutic outcomes for GBM.

Nanoplatforms for Magnetic-Photo-Heating of Thermo-Resistant Tumor Cells: Singular Synergic Therapeutic Effects at Mild Temperature.

A self-assemble amphiphilic diblock copolymer that can incorporate iron oxide nanocubes (IONCs) in chain-like assemblies as heat mediators for magnetic hyperthermia (MHT) and tuneable amounts of IR780 dye as agent for photothermal therapy (PTT) is developed. MHT-heating performance of photobeads in viscous media have the same heat performances in water at magnetic field conditions of clinical use. Thanks to IR780, the photobeads are activated by infrared laser light within the first biological window (808nm) with a significant enhancement of photo-stability of IR780 enabling the raise of the temperature at therapeutic values during multiple PTT cycles and showing unchanged optical features up to 8 days. Moreover, the photobeads fluorescent signal is preserved once internalized by glioblastoma multiforme (GBM) cells. Peculiarly, the photobeads are used as toxic agents to eradicate thermo-resistant GBM cells at mild heat, as low as 41°C, with MHT and PTT both of clinical use. Indeed, a high U87 GBM cell mortality percentage is obtained only with dual MHT/PTT while each single treatment dose not provide the same cytotoxic effects. Only for the combined treatment, the cell death mechanism is assigned to clear sign of apoptosis as observed by structural/morphological cell studies and enhanced lysosome permeability.

Tuning the physical properties of ternary alloys (NiCuCo) for in vitro magnetic hyperthermia: experimental and theoretical investigation

Most of published research on magnetic hyperthermia focused on iron oxides, ferrites, and binary alloy nanostructures, while the ternary alloys attracted much limited interest. Herein, we prepared NiCuCo ternary alloy nanocomposites with variable compositions by mechanical alloying. Physical properties were fully characterized by XRD, Rietveld analysis, XPS, SEM/EDX, TEM, ZFC/FC and H-M loops. DFT calculations were used to confirm the experimental results in terms of structure and magnetism. The results showed that the fabricated nanoalloys are face centered cubic (FCC) with average core sizes of 9–40 nm and behave as superparamagnetic with saturation in the range 4.67–42.63 emu/g. Langevin fitting corroborated the superparamagnetic behavior, while law of approach to saturation (LAS) was used to calculate the magnetic anisotropy constants. Heating effciencies were performed under an alternating magnetic field (AMF, H0 = 170 Oe and f = 332.5 kHz), and specific absorption rate (SAR) values were determined. The highest magnetic saturation (Ms), heating potentials, and SAR values were attained for Ni35Cu30Co35 containing the lowest Cu but highest Ni and Co percentages, and the least for Ni15Cu70Co15. Importantly, the nanoalloys reached the required temperatures for magnetic hyperthermia (42 °C) in relatively short times. We also showed that heat dissipiation can be simply tuned by changing many parameters such as concentration, field amplitude, and frequency. Finally, cytotoxicity viability assays against two different breast cancer cell lines treated with Ni25Cu50Co25 nanoalloy in the presence and absence of AMF were investigated. No significant decrease in cancer cell viability was observed in the absence of AMF. When tested against tumorigenic KAIMRC2 breast cancer cells under AMF, the NiCuCo nanoalloy was found to be highly potent to the cells (~ 2-fold enhancement), killing almost all the cells in short times (20 min) and clinically-safe AC magnetic fields. These findings strongly suggest that the as-prepared ternary NiCuCo nanoalloys hold great promise for potential magnetically-triggered cancer hyperthermia.

Effect of different injection strategies considering intravenous injection on combination therapy of magnetic hyperthermia and thermosensitive liposomes

Abstract The combination therapy of magnetic hyperthermia and thermosensitive liposomes (TSL) is an emerging and effective cancer treatment method. The heat generation of magnetic nanoparticles (MNPs) due to an external alternating magnetic field can not only directly damage tumor cells, but also serves as a triggering factor for the release of doxorubicin from TSL. The aim of this study is to investigate the effects in the degree of tumor cell damage of two proposed injection strategies that consider intravenous administration. Since both MNPs and TSL enter the tumor region intravenously, this study establishes a biological geometric model based on an experiment-based vascular distribution. Furthermore, this study derives the flow velocity of interstitial fluid after coupling the pressure distribution inside blood vessels and the pressure distribution of interstitial fluid, which then provides the convective velocity for the calculation of subsequent nanoparticle concentration. Different injection strategies for the proposed approach are evaluated by drug delivery result, temperature distribution, and tumor cell damage. Simulation results demonstrate that the proposed delayed injection strategy after optimization can not only result in a wider distribution for MNPs and TSL due to the sufficient diffusion time, but also improves the distribution of the temperature and drug concentration fields for the overall efficacy of combination therapy.

Synergistic effects of combined hyperthermia and electric fields treatment in non-small cell lung-cancer (NSCLC) cell lines.

Lung cancer remains a leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) being particularly challenging due to poor survival rates, emphasizing the need for new treatments. This study examined the therapeutic effects of combining hyperthermia (HT) with tumor-treating electric fields (TTF) in NSCLC. Cells were exposed to four different conditions: hyperthermia at 42°C for 30min, electric fields at 150kHz and 0.8V/cm for 24h, a combination of both treatments, or no treatment (control). Cell proliferation was measured using WST and colony-formation assays, while apoptosis, DNA damage, and repair protein levels were analyzed via Western blotting. Metastatic potential was evaluated with a transwell assay, and cell migration was assessed using the wound-healing assay. The combination therapy significantly inhibited colony formation and reduced cell migration and invasion more effectively than individual treatments. The combined treatment also enhanced apoptosis, as indicated by increased cleaved-PARP and Annexin V levels. In addition, the DNA-damage marker γ-H2AX was elevated, while BRCA1, a protein involved in DNA repair, was significantly downregulated compared to the individual treatments. These results suggest that the enhanced anticancer effects of HT and TTF are due to increased DNA damage and suppression of DNA-repair mechanisms, highlighting the potential of this combination therapy for NSCLC treatment.

Intracellular Magnetic Hyperthermia Sensitizes Sorafenib to Orthotopic Hepatocellular Carcinoma Via Amplified Ferroptosis.

Sorafenib (SRF) is recognized as the primary treatment for hepatocellular carcinoma (HCC), yet the emergence of SRF resistance in many HCC patients results in unfavorable outcomes. Enhancing the efficacy of SRF in HCC remains a significant challenge. SRF works in inducing ferroptosis, a form of cell death, in cancer cells through the inhibition of glutathione peroxidase 4 (GPX4). The effectiveness of this process is limited by the low levels of cellular iron and reactive oxygen species (ROS). A promising approach to circumvent this limitation is the use of intracellular magnetic hyperthermia (MH) mediated by magnetic iron oxide nanomaterials (MIONs). When MIONs are subjected to an alternating magnetic field (AMF), they heat up, enhancing the Fenton reaction, which in turn significantly increases the production of ROS within cells. In this study, we explore the capability of MH facilitated by high-performance ferrimagnetic vortex-domain iron oxide nanoring (FVIO) to enhance the effectiveness of SRF treatment in HCC. The increased iron uptake facilitated by FVIO significantly enhances the sensitivity of HCC cells to SRF-induced ferroptosis. Moreover, the nanoheat generated by FVIO in response to an AMF further elevates ROS levels and stimulates lipid hydroperoxide (LPO) production and GPX4 inactivation, thereby intensifying ferroptosis. Both in vitro and in vivo animal studies demonstrate that combining FVIO-mediated MH with SRF significantly reduces cell viability and inhibits tumor growth, primarily through enhanced ferroptosis, with minimal side effects. The effectiveness of this combination therapy is affected by the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine (DFO). The combination treatment of FVIO-mediated MH and SRF offers a strategy for HCC treatment by promoting accelerated ferroptosis, presenting a different perspective for the development of ferroptosis-based anticancer therapies.

Functionalized Nanomaterials In Pancreatic Cancer Theranostics And Molecular Imaging.

Pancreatic cancer (PC) is one of the most fatal malignancies in the world. This lethality persists due to lack of effective and efficient treatment strategies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive epithelial malignancy which has a high incidence rate and contributes to overall cancer fatalities. As of 2022, pancreatic cancer contributes to about 3 % of all cancers globally. Over the years, research has characterised germline predisposition, the origin cell, precursor lesions, genetic alterations, structural alterations, transcriptional changes, tumour heterogeneity, metastatic progression, and the tumour microenvironment, which has improved the understanding of PDAC carcinogenesis. By using molecular-based target therapies, these fundamental advancements support primary prevention, screening, early detection, and treatment. The focus of this review is the use of targeted nanoparticles as an alternative to conventional pancreatic cancer treatment due to the various side effects of the latter. The principles of nanoparticle based cancer therapy is efficient targeting of tumour cells via enhanced permeability and retention (EPR) effects and decrease the chemotherapy side effects due to their non-specificity. To increase the efficiency of existing therapies and modify target nanoparticles, several molecular markers of pancreatic cancer cells have been identified. Thus pancreatic cancer cells can be detected using appropriately functionalized nanoparticles with specific signalling molecules. Once cancer has been identified, these nanoparticles can kill the tumour by inducing hyperthermia, medication delivery, immunotherapy or gene therapy. As potent co-delivery methods for adjuvants and tumor-associated antigens; nanoparticles (NPs) have demonstrated significant promise as delivery vehicles in cancer therapy. This ensures the precise internalization of the functionalized nanoparticle and thus also activates the immune system effectively against tumor cells. This review also discusses the immunological factors behind the uptake of functionalized nanoparticles in cancer therapies. Theranostics, which combine imaging and therapeutic chemicals in a single nanocarrier, are the next generation of medicines. Pancreatic cancer treatment may be revolutionised by the development of a tailored nanocarrier with diagnostic, therapeutic, and imaging capabilities. It is extremely difficult to incorporate various therapeutic modalities into a single nanocarrier without compromising the individual functionalities. Surface modification of nanocarriers with antibodies or proteins will enable to attain multifunctionality which increases the efficiency of pancreatic cancer therapy.

Hyaluronic acid-coated iron oxide nanoparticles for magnetic fluid hyperthermia and methylene blue dye removal: Preparation, physicochemical characterization, and enhancing the heating efficiency

We report here the magnetic fluid hyperthermia properties of water-dispersible hyaluronic acid-coated superparamagnetic iron oxide nanoparticles (HA-MNPs), prepared using the coprecipitation technique followed by ligand exchange. The presence of the hyaluronic acid coating is confirmed using Fourier transform infrared spectroscopy. Magneto-calorimetric studies show good field-induced heating efficiency of the HA-MNPs, where a high specific absorption rate (SAR) of ∼ 315 W/gFe is obtained for ∼ 5 wt% MNP concentration when exposed to an alternating magnetic field amplitude of ∼ 33.1 kA/m at ∼ 126 kHz. The heating efficiency is found to decrease by ∼ 33.8 % after immobilization of the MNPs within an agar matrix, which is attributed to the abrogation of Brownian relaxation. When subjected to an external DC magnetic field, the MNPs form linear chain-like structures, which causes the effective anisotropy energy density to increase. Magneto-calorimetric studies on agar-based oriented samples reveal a ∼ 19.5 % enhancement in SAR, thereby partly compensating for the loss in heating efficiency due to an increase in medium viscosity. The orientational ordering-induced enhancement in SAR is also verified using sweeping rate modified Stoner-Wohlfarth model-based calculations. In vitro cyto-toxicity studies on the HeLa cell lines reveal good cyto-compatibility of the MNPs. The negative charge on the surface of HA-coated MNPs is exploited to remove the cationic methylene blue dye from the aqueous medium, where the dye molecules are found to be physisorbed on the surface of the MNPs. The experimental findings clearly show the high induction heating efficiency, cyto-compatibility, and cationic dye-adsorption efficiency of the prepared HA-MNPs, thereby indicating the suitability of these MNPs for multi-functional applications like magnetic fluid hyperthermia and waste-water purification.

Comparisons of computer simulations and experimental data for capacitive hyperthermia using different split-phantoms

Introduction Several positive clinical trials have demonstrated that capacitive hyperthermia (CHT) improves the effectiveness of radiation therapy for the treatment of various cancer entities. However, the ability of CHT to induce significant heating throughout the body is under debate. Objectives To perform a pilot study involving comparisons of computer simulations and experimental data using different split-phantoms to validate hyperthermia treatment modeling for pre-planning for a clinical CHT system and to investigate the feasibility of split-phantom measurements in capacitive hyperthermia. Materials and methods The CHT system EHY-2030 (Oncotherm, Budapest, Hungary) was used. The system provides two electrode sizes, but only the smaller electrode, indicated as D200 electrode, was investigated in this pilot study. Horizontally and vertically splittable, different multi-slice phantoms with dielectric material properties simulating muscle and electrically low conductive fat were produced and heated. During the heating procedure, temperature-time curves were measured, and thermal images were captured. Specific absorption rate values were derived from the temperature rise (TR) values. Concomitantly, computer field simulations utilizing a detailed CAD-based model of the CHT system were performed using the simulation platform Sim4Life and compared with measurements. Results For the investigated electrode D200 the system power of 75 W was applied, which is half of the maximum power of 150 W and lies in the range of usual values for this electrode applied in patient treatments in our clinic. For 75 W, a heating of 3.6 °C in 6 min in a depth of 1 cm in an agar-based, muscle tissue-equivalent phantom was achieved. The addition of a 1 cm thick, synthetic, low dielectric fat layer reduced the TR up until a depth of 8.5 cm by on average around 38% (from 8.5 cm onwards the absolute local TR is similar, deviations are ≤0.1 °C). In terms of point-to-point absolute SAR comparison (without any normalization), up to a depth of 11 cm in the phantoms central vertical plot, the simulation differs from the measured TR points by on average 25% (ranging from 7% to 36%) for the homogeneous phantom and by on average 43% (ranging from 26% to 60%) for the inhomogeneous phantom. Conclusion Computer simulations and experimental data were compared for the CHT system EHY-2030 using the D200 electrode, applying a thermal imaging technique for different vertically splittable phantoms. This pilot study data can be used as a guidance regarding the expected heating for this commonly used electrode size but also to further elucidate the significance of non-thermal anticancer effects. Further studies are needed for different sizes and geometries of electrodes and phantoms.

Combination of magnetic hyperthermia and gene therapy for breast cancer.

This study presented a novel breast cancer therapy model that uses magnetic field-controlled heating to trigger gene expression in cancer cells. We created silica- and amine-modified superparamagnetic nanoparticles (MSNP-NH2) to carry genes and release heat under an alternating current (AC) magnetic field. The heat-inducible expression plasmid(pHSP-Azu) was designed to encode anti-cancer azurin and was delivered by magnetofection. MCF-7 cells demonstrated over 93% cell viability and 12% transfection efficiency when exposed to 75µg/ml of MSNP-NH2, 3µg of DNA, and PEI at a 0.75 PEI/DNA ratio (w: w), unlike non-tumorigenic cells (MCF-10A). Magnetic hyperthermia (MHT) increased azurin expression by heat induction, leading to cell death in dual ways. The combination of MHT and heat-regulated azurin expression induced cell death, specifically in cancer cells, while having negligible effects on MCF-10A cells. The proposed strategy clearly shows that simultaneous use of MHT and MHT-induced azurin gene expression may selectively target and kill cancer cells, offering a promising direction for cancer therapy.

Ranking Magnetic Colloid Performance for Magnetic Particle Imaging and Magnetic Particle Hyperthermia

AbstractMagnetic particle imaging (MPI) is an emerging modality that can address longstanding technological challenges encountered with magnetic particle hyperthermia (MPH) cancer therapy. MPI is a tracer technology compatible with MPH for which magnetic nanoparticles (MNPs) provide signal for MPI and heat for MPH. Identifying whether a specific MNP formulation is suitable for both modalities is essential for clinical implementation. Current models predict that functional requirements of each modality impose conflicting demands on nanoparticle magnetic properties. This objective here is to develop a measurement and ranking scheme based on end‐use performance to streamline evaluation of candidate MNP formulations. The measured MPI point‐spread function (PSF) and specific loss power (SLP) is combined to generate a single numerical value for comparison on a relative ranking scale, or figure of merit (FoM). 12 aqueous iron‐containing formulations are evaluated, including FDA‐approved (parenteral) iron‐containing colloids. MNPs with high (Synomag‐D70: 123.4), medium (Synomag‐D50: 63.2), and low (NanoXact: 0.147) FoM values are selected for in vivo validation of the selection scheme in subcutaneous 4T1 tumors. Results demonstrate that the proposed ranking accurately assessed the relative performance of MNPs for MPI and MPH. Data demonstrated that image quality and tumor temperature rise increased with FoM ranking, validating predictions. It isshown that the MPI signal correlated with MNP concentration in tissue. Computational heat transfer models anchored on tumor MPI data harmonized with experimental results to within an average of 2 °C when MNP content estimated from MPI data is included. Computational studies emphasized the importance of post‐injection MNP quantitation and MPI spatial resolution.

Dual Frequency-Regulated Magnetic Vortex Nanorobots Empower Nattokinase for Focalized Microvascular Thrombolysis.

Magnetic nanorobots are emerging players in thrombolytic therapy due to their noninvasive remote actuation and drug loading capabilities. Although the nanorobots with a size under 100 nm are ideal to apply in microvascular systems, the propulsion performance of nanorobots is inevitably compromised due to the limited response to magnetic fields. Here, we demonstrate a nattokinase-loaded magnetic vortex nanorobot (NK-MNR) with an average size around 70 nm and high saturation magnetization for mechanical propelling and thermal responsive thrombolysis under a magnetic field with dual frequencies. The nanorobots are stable in suspension and undergo the magneto-steered assembly into chain-like NK-MNRs, which are regulated to generate magnetic forces to mechanically damage and penetrate the thrombus by the low-frequency rotating magnetic field. Synergistically, enhanced magnetic hyperthermia is triggered by an alternating magnetic field of high frequency, enabling heat-induced NK release and fibrinolysis. In this dual frequency-regulated magnetothrombolysis (fRMT) strategy, nanorobots collaborate under the dual magnetic energy conversion model to achieve the vasculature recanalization rate of 81.0% in thrombotic mice. Overall, the nanorobot with the special magnetic vortex property and multimodel controls is a promising nanoplatform for in vivo focalized microvascular thrombolysis.