Alternating Magnetic Field Research Articles

Recent Developments in Magnetic Hyperthermia Therapy (MHT) and Magnetic Particle Imaging (MPI) in the Brain Tumor Field: A Scoping Review and Meta-Analysis.

Magnetic hyperthermia therapy (MHT) is a promising treatment modality for brain tumors using magnetic nanoparticles (MNPs) locally delivered to the tumor and activated with an external alternating magnetic field (AMF) to generate antitumor effects through localized heating. Magnetic particle imaging (MPI) is an emerging technology offering strong signal-to-noise for nanoparticle localization. A scoping review was performed by systematically querying Pubmed, Scopus, and Embase. In total, 251 articles were returned, 12 included. Articles were analyzed for nanoparticle type used, MHT parameters, and MPI applications. Preliminary results show that MHT is an exciting treatment modality with unique advantages over current heat-based therapies for brain cancer. Effective application relies on the further development of unique magnetic nanoparticle constructs and imaging modalities, such as MPI, that can enable real-time MNP imaging for improved therapeutic outcomes.

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.

Magnetic field modulation of high spin hexa-coordinated iron sites to enhance catalytic activity

The external alternating magnetic field (AMF) strategy is the most promising research topic to solve the bottleneck of catalyst activity enhancement. However, the mechanism between the arrangement of the spin electrons under the AMF and the catalytic activity enhancement for water splitting is still unclear. Herein, we synthesize Fe3O4@CNTs heterostructure as a research model and resolve the mechanism by system theoretical analysis and in-situ Raman characterization. The multiple orbital interactions of σ(dz2, pz, s) and π(dxz-px, dyz-py) promote the hexa-coordinated Feoct for both the reductive HER and oxidative OER processes. The AMF excites the transition from low to high spin configurations of the Feoct sites, which accelerates charge transfer of unpaired d electrons and optimizes adsorption and desorption interactions to intermediates during the reaction processes, resulting in a significant enhancement of the electrocatalytic activity (HER: 32 mV at 10 mA cm−2, OER: 179 mV at 100 mA cm−2).

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.

Fabrication of PEGylated SPIONs-Loaded Niosome for Codelivery of Paclitaxel and Trastuzumab for Breast Cancer Treatment: In Vivo Study.

There is a growing appeal for engineering drug delivery systems for controlled and local drug delivery. Conjugation of antibodies on the nanocarriers for targeted chemotherapeutic drugs has always been one of the main techniques. This work aims to develop a polycaprolactone/chitosan electrospun mat incorporated with paclitaxel/Fe3O4-loaded niosomes (SPNs) decorated with trastuzumab (TbNs) for cancer therapy. SPNs and TbNs were analyzed by DLS, zeta potential, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. Fabricated mats with distinct concentrations of TbNs were classified into four groups (G0 (0), G1 (1), G2 (2.5), and G3 (5%)) and were studied physicochemically, mechanically, and biologically. Paclitaxel release was also studied for 7 days under an alternative magnetic field (AMF). The optimized mat was nominated for an in vivo study to evaluate its tumor growth inhibition. Based on the results, the TbNs had a spherical core and shell morphology with a smooth surface. The zeta potential and the mean size of TbNs were equal to -14.7 mV and 221 nm. TbNs did not affect the morphology and quality of nanofibers, but in general, the presence of TbNs increased the elastic modulus, water uptake, and degradation. Regarding the release study, AMF showed a significant increase in accelerating paclitaxel release from mats, and most releases belonged to the mat with 5% of TbNs. Results from the in vivo study showed the effective and synergistic effects of AMF on drug release and significant tumor growth inhibition. To summarize, the proposed nanocarrier under AMF can be a good candidate for cancer therapy.

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).

Investigating antitumor therapeutic efficacy using magnetic hyperthermia of Fe3O4 nanoparticles

Four sets of Fe3O4 nanoparticles were synthesized using a one-pot hydrothermal method using ethylene glycol (EG) and water reaction mixture. The EG coated Fe3O4 nanoparticles were characterized using XRD (X-ray diffraction) and DLS (dynamic light scattering). The nanoparticles hydrodynamic sizes are in the range 60-100 nm and showed good dispersibility in water and cellular medium without any aggregation. The specific absorption rate (SAR) under an alternating magnetic field (AMF) was measured to evaluate the magneto hyperthermic effect of the nanoparticles under field amplitudes of 51.85, 43.87, 35.89, and 27.92 kA/m and field frequencies in the range 384.5-167.30 kHz. The nanoparticles synthesized using 30% EG showed the highest SAR value of 372.95 W/g, whereas the particles synthesized using 70% EG showed a SAR value of 217.12 W/g. SAR values show a linear dependency on the AC frequency whereas the field amplitude displayed a nonlinear effect on the SAR. Breast cancer cells (MDA) treated with the nanoparticles for 30 minutes under an AMF of frequency of 384.5 kHz and strength of 24.67 kA/m showed a 50% decrease in cell viability. The cellular viability further decreased to 25% after 24 h treatment under the AMF which is remarkable for the therapeutic application of the nanoparticles. The apoptotic cell death showed a dependency on the AMF frequency and strength combinations.

Fe3O4@Chitosan@ZIF-8@RVG29, an anti-glioma nanoplatform guided by fixed and activated by alternating magnetic field

There is considerable interest in developing anti-glioma nanoplatforms. They make the all-in-one combination of therapies possible. Here we show how the selective Glioblastoma multiforme (GBM) cell killing of the here-established nanoplatforms increased after each coating and how the here-established vibration-inducing Alternating magnetic field (AMF) decreased the treatment time from 72 h to 30 s. Thanks to their magnetite core, these nanoplatforms can be guided to the tumor's specific site by a Fixed magnetic field, they bypass the Blood–Brain Barrier (BBB) and accumulate at the tumor site thanks to the RVG29 bonding to the G-protein on the ion-gated channel receptor known as the nicotinic acetylcholine receptor (nAchR), which expresses on BBB cells and overexpresses on GBM cells, and thanks to the positive charge gained by both chitosan and RVG29's peptide. Both ZIF-8 and its mediate adherence, Chitosan increases the drug loading capacity that stimuli response to the tumor's acidic environment. The Zn2+ ions generated from ZIF-8 sustained degradation in such an environment kill the GBM cells. Dynamic Light Scattering (DLS) evaluated these nanoplatform's mean size 155 nm indicating their almost optimum size for brain applications. Based on their elements' intrinsic properties, these nanoplatforms can enhance and combine other adjuvant therapies.

Abstract 395: An alternating magnetic field suppresses tumor growth

Abstract Application of physical forces, ranging from ultrasound to electric field, is recommended in various clinical practice guidelines, including those for bone fracture or cancer treatment. However, mechanistic information for such treatments has been poorly provided, due to the lack of comprehensive study model. Here, we show an alternating magnetic field (AMF) per se exhibits direct anti-cancer effect through enhancing oxidative phosphorylation (OXPOHS) and thus metabolic reprograming. Proliferation of human glioblastoma cells (U87 and LN229), but not normal human astrocytes (NHA), was inhibited upon exposure to AMF within the narrow frequency range. Extracellular acidification rate was decreased while oxygen consumption was increased. These data indicated that AMF induced metabolic reprograming. This was accompanied by increased reactive oxygen species (ROS) production. Mouse models grafted with human glioblastoma cells showed that AMF exposure, 30 minutes per day for two weeks, suppressed the tumor growth and prolonged the overall survival. Our results suggest that the AMF exposure may be a simple strategy to inhibit cancer cell growth by utilizing oxidative stress via metabolic reprograming. Citation Format: Masanari Umemura, Taisuke Akimoto, Rafikul Islam, Kazuhito Kishi, Akane Nagasako, Rina Nakakaji, Takashi Yamaguchi, Yuto Mizuno, Soichiro Ishikawa, Tetsuya Yamamoto, Yoshihiro Ishikawa. An alternating magnetic field suppresses tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 395.

Heating ability of amine functionalized Fe3O4 as a function of field amplitude and frequency for hyperthermia application

The functionalization of magnetic nanoparticles (MNPs) is crucial for their biomedical applications such as magnetic hyperthermia, which attracted attention in recent years as a promising alternative or complementary therapy to traditional cancer treatments. Here, we investigate a synthetic approach based on the hydrothermal process for the amine-functionalized magnetite (Fe3O4-NH2) MNPs for possible use in hyperthermia. The characterization of coated MNPs by FTIR confirms the functionalization with the amine group, while the XRD shows how the magnetite phase was formed. Magnetic measurements of both coated and uncoated MNPs at room temperature revealed their ferrimagnetic behavior. It was found from magnetic hyperthermia measurements under an alternating magnetic field (AMF) that functionalized with amine MNPs reach hyperthermia temperatures (42 °C)) in relatively short times (around 10 min.) with a adequate value of sample absorption rate (SAR)in the range between 33 to 45 W g–1. The (NH2) groups on the surface of the (Fe3O4) nanoparticles prepared by hydrothermal process make them amenable to further functionalization with various biomolecules. This enables the nanoparticles to be tailored for specific applications, such as drug delivery or targeting specific cells or tissues. Moreover, the appropriate crystallinity combined with the relatively adequate heating ability and adequate saturation suggest that the functionalized MNPs are promising for hyperthermia application.

Magnetic natural lipid nanoparticles for oral treatment of colorectal cancer through potentiated antitumor immunity and microbiota metabolite regulation

The therapeutic efficacy of oral nanotherapeutics against colorectal cancer (CRC) is restricted by inadequate drug accumulation, immunosuppressive microenvironment, and intestinal microbiota imbalance. To overcome these challenges, we elaborately constructed 6-gingerol (Gin)-loaded magnetic mesoporous silicon nanoparticles and functionalized their surface with mulberry leaf-extracted lipids (MLLs) and Pluronic F127 (P127). In vitro experiments revealed that P127 functionalization and alternating magnetic fields (AMFs) promoted internalization of the obtained P127-MLL@Gins by colorectal tumor cells and induced their apoptosis/ferroptosis through Gin/ferrous ion-induced oxidative stress and magneto-thermal effect. After oral administration, P127-MLL@Gins safely passed to the colorectal lumen, infiltrated the mucus barrier, and penetrated into the deep tumors under the influence of AMFs. Subsequently, the P127-MLL@Gin (+ AMF) treatment activated antitumor immunity and suppressed tumor growth. We also found that this therapeutic modality significantly increased the abundance of beneficial bacteria (e.g., Bacillus and unclassified-c-Bacilli), reduced the proportions of harmful bacteria (e.g., Bacteroides and Alloprevotella), and increased lipid oxidation metabolites. Strikingly, checkpoint blockers synergistically improved the therapeutic outcomes of P127-MLL@Gins (+ AMF) against orthotopic and distant colorectal tumors and significantly prolonged mouse life spans. Overall, this oral therapeutic platform is a promising modality for synergistic treatment of CRC.

Strain engineering induced surfacial catalytic amorphous Ni3C with room temperature ferromagnetism for magnetic heating enhancement of overall water-splitting

Amorphous materials have been recognized as highly active electrocatalysts due to their abundant active sites stems from unsaturated chemical bonds. In addition, the application of alternating magnetic fields (AMF) to achieve magnetic heating effect has gradually become an important means to improve the performance of magnetic catalysts. Here, we have successfully realized the surfacial amorphization of confined Ni3C nanoparticles by using interfacial strain engineering. As expected, the surfacial amorphized Ni3C nanoparticles exhibit remarkable properties in electrochemical water-splitting. More importantly, magnetic measurements show that the surfacial amorphized Ni3C nanoparticles have room temperature ferromagnetism, which is consistent with our theoretical calculation results. Accordingly, under AMF stimulation, its overall water-splitting performance is further greatly improved as the result of magnetic heating effect associated with Néel relaxation. This work provides a new strategy for the development of highly efficient surfacial amorphized catalysts, and promotes the application of magnetothermal technology in amorphous catalysis.

Evaluation of Antiproliferative Properties of CoMnZn-Fe2O4 Ferrite Nanoparticles in Colorectal Cancer Cells.

The PEG-coated ferrite nanoparticles Co0.2Mn0.6Zn0.2Fe2O4 (X1), Co0.4Mn0.4Zn0.2Fe2O4 (X2), and Co0.6Mn0.2Zn0.2Fe2O4 (X3) were synthesized by the coprecipitation method. The nanoparticles were characterized by XRD, Raman, VSM, XPS, and TEM. The magnetic hyperthermia efficiency (MH) was determined for PEG-coated nanoparticles using an alternating magnetic field (AMF). X2 nanoparticles displayed the highest saturation magnetization and specific absorption rate (SAR) value of 245.2 W/g for 2 mg/mL in a water medium. Based on these properties, X2 nanoparticles were further evaluated for antiproliferative activity against HCT116 cells at an AMF of 495.25 kHz frequency and 350 G strength, using MTT, colony formation, wound healing assays, and flow cytometry analysis for determining the cell viability, clonogenic property, cell migration ability, and cell death of HCT116 cells upon AMF treatment in HCT116 cells, respectively. We observed a significant inhibition of cell viability (2% for untreated control vs. 50% for AMF), colony-forming ability (530 cells/colony for untreated control vs. 220 cells/colony for AMF), abrogation of cell migration (100% wound closure for untreated control vs. 5% wound closure for AMF), and induction of apoptosis-mediated cell death (7.5% for untreated control vs. 24.7% for AMF) of HCT116 cells with respect to untreated control cells after AMF treatment. Collectively, these results demonstrated that the PEG-coated (CoMnZn-Fe2O4) mixed ferrite nanoparticles upon treatment with AMF induced a significant antiproliferative effect on HCT116 cells compared with the untreated cells, indicating the promising antiproliferative potential of the Co0.4Mn0.4Zn0.2Fe2O4 nanoparticles for targeting colorectal cancer cells. Additionally, these results provide appealing evidence that ferrite-based nanoparticles using MH could act as potential anticancer agents and need further evaluation in preclinical models in future studies against colorectal and other cancers.

Magnetic Hyperthermia Therapy for High-Grade Glioma: A State-of-the-Art Review.

Magnetic hyperthermia therapy (MHT) is a re-emerging treatment modality for brain tumors where magnetic nanoparticles (MNPs) are locally delivered to the brain and then activated with an external alternating magnetic field (AMF) to generate localized heat at a site of interest. Due to the recent advancements in technology and theory surrounding the intervention, clinical and pre-clinical trials have demonstrated that MHT may enhance the effectiveness of chemotherapy and radiation therapy (RT) for the treatment of brain tumors. The future clinical success of MHT relies heavily on designing MNPs optimized for both heating and imaging, developing reliable methods for the local delivery of MNPs, and designing AMF systems with integrated magnetic particle imaging (MPI) for use in humans. However, despite the progression of technological development, the clinical progress of MHT has been underwhelming. This review aims to summarize the current state-of-the-art of MHT and offers insight into the current barriers and potential solutions for moving MHT forward.

On‐Demand Magnetically‐Activated Drug Delivery from Additively Manufactured Porous Bone Implants to Tackle Antibiotic‐Resistant Infections

AbstractThis study proposes a new concept for an on‐demand drug releasing device intended for integration into additively manufactured (i.e., 3D printed) orthopedic implants. The system comprises a surface with conduits connected to a subsurface reservoir used for storage and on‐demand release of antimicrobial agents, covered with a cap that prevents the antibacterial agents from being released until alternating magnetic field (AMF) raises the temperature of the cap, thus, releasing the stored drug. To demonstrate this concept, Ti6Al4V specimens are directly 3D printed using selective laser melting and their surface, reservoirs, and drug releasing properties are characterized. A new synthetic antimicrobial peptide, SAAP‐148, is thereafter tested for its cytotoxic, osteogenic, and immunomodulatory effects at concentrations relevant for its minimal bactericidal concentration (MBC) and is compared with its natural analogue, LL‐37. The results showed that AMF successfully activated the release from the 3D printed loaded samples. Both peptides demonstrated to be non‐cytotoxic within the MBC levels for macrophages and preosteoblasts and did not influence their osteoimmunomodulatory behavior. The findings of this study indicate that the proposed concept is technically feasible and has the potential to be used for the development of bone implants with on‐demand delivery systems to fight IAI without systemic or continuous local release of antibiotics.

Smart composite scaffold to synchronize magnetic hyperthermia and chemotherapy for efficient breast cancer therapy

Combination of different therapies is an attractive approach for cancer therapy. However, it is a challenge to synchronize different therapies for maximization of therapeutic effects. In this work, a smart composite scaffold that could synchronize magnetic hyperthermia and chemotherapy was prepared by hybridization of magnetic Fe3O4 nanoparticles and doxorubicin (Dox)-loaded thermosensitive liposomes with biodegradable polymers. Irradiation of alternating magnetic field (AMF) could not only increase the scaffold temperature for magnetic hyperthermia but also trigger the release of Dox for chemotherapy. The two functions of magnetic hyperthermia and chemotherapy were synchronized by switching AMF on and off. The synergistic anticancer effects of the composite scaffold were confirmed by in vitro cell culture and in vivo animal experiments. The composite scaffold could efficiently eliminate breast cancer cells under AMF irradiation. Moreover, the scaffold could support proliferation and adipogenic differentiation of mesenchymal stem cells for adipose tissue reconstruction after anticancer treatment. In vivo regeneration experiments showed that the composite scaffolds could effectively maintain their structural integrity and facilitate the infiltration and proliferation of normal cells within the scaffolds. The composite scaffold possesses multi-functions and is attractive as a novel platform for efficient breast cancer therapy.

Injectable Magnetic Hydrogel Filler for Synergistic Bone Tumor Hyperthermia Chemotherapy.

The therapeutic efficacy of bone tumor treatment is primarily limited by inadequate tumor resection, resulting in recurrence and metastasis, as well as the deep location of tumors. Herein, an injectable doxorubicin (DOX)-loaded magnetic alginate hydrogel (DOX@MAH) was developed to evaluate the efficacy of an alternating magnetic field (AMF)-responsive, chemothermal synergistic therapy for multimodality treatment of bone tumors. The prepared hydrogel exhibits a superior drug-loading capacity and a continuous DOX release. This multifunctionality can be attributed to the combined use of DOX for chemotherapy and iron oxide nanoparticle-containing alginate hydrogels as magnetic hyperthermia agents to generate hyperthermia for tumor elimination without the limit on penetration depth. Moreover, the hydrogel can be formed when in contact with the calcium ions, which are abundant in bone tissues; therefore, this hydrogel could perfectly fit the bone defects caused by the surgical removal of the bone tumor tissue, and the hydrogel could tightly attach the surgical margin of the bone to realize a high efficacy residual tumor tissue elimination treated by chemothermal synergistic therapy. The hydrogel demonstrates excellent hyperthermia performance, as evidenced by in vitro cytotoxicity tests on tumor cells. These tests reveal that the combined therapy based on DOX@MAH under AMF significantly induces cell death compared to single magnetic hyperthermia or chemotherapy. In vivo antitumor effects in tumor-bearing mice demonstrate that DOX@MAH injection at the tumor site effectively inhibits tumor growth and leads to tumor necrosis. This work not only establishes an effective DOX@MAH system as a synergistic chemothermal therapy platform for treating bone tumors but also sheds light on the application of alginate to combine calcium ions of the bone to treat bone defect diseases.

Smart Design of ZnFe and ZnFe@Fe Nanoparticles for MRI-Tracked Magnetic Hyperthermia Therapy: Challenging Classical Theories of Nanoparticles Growth and Nanomagnetism.

Iron Oxide Nanoparticles (IONPs) hold the potential to exert significant influence on fighting cancer through their theranostics capabilities as contrast agents (CAs) for magnetic resonance imaging (MRI) and as mediators for magnetic hyperthermia (MH). In addition, these capabilities can be improved by doping IONPs with other elements. In this work, the synthesis and characterization of single-core and alloy ZnFe novel magnetic nanoparticles (MNPs), with improved magnetic properties and more efficient magnetic-to-heat conversion, are reported. Remarkably, the results challenge classical nucleation and growth theories, which cannot fully predict the final size/shape of these nanoparticles and, consequently, their magnetic properties, implying the need for further studies to better understand the nanomagnetism phenomenon. On the other hand, leveraging the enhanced properties of these new NPs, successful tumor therapy by MH is achieved following their intravenous administration and tumor accumulation via the enhanced permeability and retention (EPR) effect. Notably, these results are obtained using a single low dose of MNPs and a single exposure to clinically suitable alternating magnetic fields (AMF). Therefore, as far as the authors are aware, for the first time, the successful application of intravenously administered MNPs for MRI-tracked MH tumor therapy in passively targeted tumor xenografts using clinically suitable conditions is demonstrated.

Ion-interferential cell cycle arrest for melanoma treatment based on magnetocaloric bimetallic-ion sustained release hydrogel

Melanoma treatment has been revolutionized with the development of targeted therapies and immunotherapies, which shows a positive influence on the patients. However, the long-term efficaciousness of such therapy is restricted by side effects, limited clinical effects as well as quick resistance to treatment. In this work, we prepared magnetocaloric carrier-free bimetallic hydrogels, named manganese-iron oxide nanocubes@polyethylene glycol-hydrogels (MFO@PEG-Gels), to realize ion-interferential cell cycle arrest for melanoma treatment. In detail, the tumor site was exposed to alternating magnetic field (AMF) after intratumorally injected MFO@PEG-Gels, which generated hyperthermia and promoted the sol-gel phase transition for MFO sustained release. Under the tumor microenvironment, hydrogen peroxide triggered MFO degradation to induce Mn2+ and Fe3+ release. On one hand, Mn2+ blocked G1/S phase through the activation of p27 pathway. On the other hand, Fe3+ could arrest the G2/M phase by upregulating the polo-like kinase 4 (PLK4) expression as well as inhibiting autolysosome formation to achieve the enhanced cell cycle arrest, thereby promoting the apoptosis of melanoma cells. In summary, this study proposed ion-interferential cell cycle arrest strategy by a multifunctional and injectable magnetic bimetallic hydrogel for melanoma treatment, which provided a secure and sustainable regimen for enhancing anti-tumor efficacy.

Hybrid hydrogels support neural cell culture development under magnetic actuation at high frequency

The combination of hydrogels and magnetic nanoparticles, scarcely explored to date, offers a wide range of possibilities for innovative therapies. Herein, we have designed hybrid 3D matrices integrating natural polymers, such as collagen, chitosan (CHI) and hyaluronic acid (HA), to provide soft and flexible 3D networks mimicking the extracellular matrix of natural tissues, and iron oxide nanoparticles (IONPs) that deliver localized heat when exposed to an alternating magnetic field (AMF). First, colloidally stable nanoparticles with a hydrodynamic radius of ∼20 nm were synthesized and coated with either CHI (NPCHI) or HA (NPHA). Then, collagen hydrogels were homogeneously loaded with these coated-IONPs resulting in soft (E0 ∼ 2.6 kPa), biodegradable and magnetically responsive matrices. Polymer-coated IONPs in suspension preserved primary neural cell viability and neural differentiation even at the highest dose (0.1 mg Fe/mL), regardless of the coating, even boosting neuronal interconnectivity at lower doses. Magnetic hydrogels maintained high neural cell viability and sustained the formation of highly interconnected and differentiated neuronal networks. Interestingly, those hydrogels loaded with the highest dose of NPHA (0.25 mgFe/mg polymer) significantly impaired non-neuronal differentiation with respect to those with NPCHI. When evaluated under AMF, cell viability slightly diminished in comparison with control hydrogels magnetically stimulated, but not compared to their counterparts without stimulation. Neuronal differentiation under AMF was only affected on collagen hydrogels with the highest dose of NPHA, while non-neuronal differentiation regained control values. Taken together, NPCHI-loaded hydrogels displayed a superior performance, maybe benefited from their higher nanomechanical fluidity. Statement of significanceHydrogels and magnetic nanoparticles are undoubtedly useful biomaterials for biomedical applications. Nonetheless, the combination of both has been scarcely explored to date. In this study, we have designed hybrid 3D matrices integrating both components as promising magnetically responsive platforms for neural therapeutics. The resulting collagen scaffolds were soft (E0 ∼ 2.6 kPa) and biodegradable hydrogels with capacity to respond to external magnetic stimuli. Primary neural cells proved to grow on these substrates, preserving high viability and neuronal differentiation percentages even under the application of a high-frequency alternating magnetic field. Importantly, those hydrogels loaded with chitosan-coated iron oxide nanoparticles displayed a superior performance, likely related to their higher nanomechanical fluidity.