Application Of Alternating Magnetic Field Research Articles

Beyond Traditional Hyperthermia: In Vivo Cancer Treatment with Magnetic-Responsive Mesoporous Silica Nanocarriers

In this study, we present an innovation in the tumor treatment in vivo mediated by magnetic mesoporous silica nanoparticles. This device was built with iron oxide magnetic nanoparticles embedded in a mesoporous silica matrix and coated with an engineered thermoresponsive polymer. The magnetic nanoparticles act as internal heating sources under an alternating magnetic field (AMF) that increase the temperature of the surroundings, provoking the polymer transition and consequently the release of a drug trapped inside the silica pores. By a synergic effect between the intracellular hyperthermia and chemotherapy triggered by AMF application, significant tumor growth inhibition was achieved in 48 h after treatment. Furthermore, the small magnetic loading used in the experiments indicates that the treatment is carried out without a global temperature rise of the tissue, which avoids the problem of the necessity to employ large amounts of magnetic cores, as is common in current magnetic hyperthermia.

Combining CXCR4-targeted and nontargeted nanoparticles for effective unassisted in vitro magnetic hyperthermia.

The use of targeted nanoparticles for magnetic hyperthermia (MHT) increases MHT selectivity, but often at the expense of its effectiveness. Consequently, targeted MHT is typically used in combination with other treatment modalities. This work describes an implementation of a highly effective monotherapeutic in vitro MHT treatment based on two populations of magnetic particles. Cells were sequentially incubated with two populations of magnetic particles: nonfunctionalized superparamagnetic nanoparticles and anti-CXCR4-functionalized particles. After removing the excess of free particles, an alternating magnetic field (AMF) was applied to produce MHT. The induced cytotoxicity was assessed at different time-points after AMF application. Complete loss of cell viability was observed 72 h after MHT when the iron loading of the anti-CXCR4-functionalized particles was boosted by that of a nontargeted population. Additionally, induction of necrosis resulted in more efficient cell death than did induction of apoptosis. Achieving a uniquely high effectiveness in monotherapeutic MHT demonstrates the potential of this approach to achieve complete loss of viability of cancer cells while avoiding the side effects of dual-treatment strategies that use MHT only as a sensitizing therapy.

Prolonged heating of Fe3O4–Au hybrid nanoparticles in a radiofrequency solenoid coil

We report the hyperthermia properties of Fe3O4–Au hybrid nanoparticles (HNPs) under a biocompatible alternating magnetic field (AMF) of 1.5 kAm−1 and 200kHz. The HNPs were prepared by growing Au nanoparticles (AuNPs) with an average diameter of 3nm on the surface of Fe3O4 magnetic nanoparticles (MNPs) with an average diameter of 10nm. The structural properties were determined by transmission electron microscopy (TEM), dynamic light scattering (DLS), and X-ray diffraction (XRD). Under the AMF, the initial heating rate of the HNPs solution was lower than that of the MNPs solution because HNPs have a reduced saturation magnetization (Ms) value compared to MNPs. The continued AMF application increased the temperature of the HNPs solution steadily while the MNPs solution reached a thermal equilibrium. The heating effect of AuNPs conjugated to diamagnetic and non-conductive SiO2 nanoparticles (SiO2-AuNPs) was demonstrated under the same AMF condition, which suggests that the prolonged heating of HNPs can be attributed to the additional heating of AuNPs in the radiofrequency (RF) solenoid coil.

Naturally Derived Iron Oxide Nanowires from Bacteria for Magnetically Triggered Drug Release and Cancer Hyperthermia in 2D and 3D Culture Environments: Bacteria Biofilm to Potent Cancer Therapeutic.

Iron oxide nanowires produced by bacteria (Mariprofundus ferrooxydans) are demonstrated as new multifunctional drug carriers for triggered therapeutics release and cancer hyperthmia applications. Iron oxide nanowires are obtained from biofilm waste in the bore system used to pump saline groundwater into the River Murray, South Australia (Australia) and processed into individual nanowires with extensive magnetic properties. The drug carrier capabilities of these iron oxide nanowires (Bac-FeOxNWs) are assessed by loading anticancer drug (doxorubicin, Dox) followed by measuring its elution under sustained and triggered release conditions using alternating magnetic field (AMF). The cytotoxicity of Bac-FeOxNWs assessed in 2D (96 well plate) and 3D (Matrigel) cell cultures using MDA-MB231-TXSA human breast cancer cells and mouse RAW 264.7 macrophage cells shows that these Bac-FeOxNWs are biocompatible even at concentrations as high as 250 μg/mL after 24 h of incubation. Finally, we demonstrate the capabilities of Bac-FeOxNWs as potential hyperthermia agent in 3D culture setup. Application of AMF increased the local temperature by 14 °C resulting in approximately 34% decrease in cell viability. Our results demonstrate that these naturally produced nanowires in the form of biofilm can efficiently act as drug carriers with triggered payload release and magnetothermal heating features for potential anticancer therapeutics applications.

Elaboration of magneto-thermally recyclable nanosorbents for remote removal of toluene in contaminated water using magnetic hyperthermia

Magnetic nanosorbents are novel materials that have been impacting various applications in environmental fields, including the detection of pollutants and remediation of polluted environments. In this work, the thermal heating effect caused by the interaction of nanoparticles’ magnetic moments with an alternating magnetic field (AMF) – magnetic hyperthermia – is proposed as proof of a concept to illustrate the remote controlled recycling of magnetic nanosorbents during the treatment of water containing toluene, a potentially toxic and volatile contaminant. Nanosorbents were synthesized by functionalization of ∼15nm coprecipitated cobalt/manganese mixed ferrite with polydimethylsiloxane. Structural, chemical, and magnetic characteristics of the nanosized adsorbent were investigated by elemental analysis (ICP-OES), X-ray diffractometry (XRD), high resolution transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FTIR) and vibrating sample magnetometry (VSM). Batch experiments indicated that nanoadsorbents, which can be magnetically recovered, exhibit high adsorption affinity for toluene in aqueous solution (∼325mg/g) and that adsorption follows the Langmuir model. Moreover, application of AMF resulted in uniform heating within the nanosorbents (after being magnetically separated from the contaminated water) and triggered toluene desorption/evaporation, leading to accelerated release of pollutants from the nanosorbent, improving its reusability; even after seven cycles the removal efficiency was quite high (83%).

Abstract 4548: Simultaneous hyperthermic-chemotherapy for glioblastoma using a single anti-cancer compound with intrinsic magnetism

Abstract Background: Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor in humans. In spite of advances in treatment strategies, survival rate of GBM remains poor. We have recently reported a novel anti-cancer compound with intrinsic magnetism(EI236). In addition to its anti-cancer effect, EI236 generates a large amount of heat upon an alternating magnetic field (AMF) application because of its magnetism, i.e., hyperthermic effect. In this study, we have examined the effect of EI236 on human GBM in vitroand vivo. Materials and Methods: Human GBM cell lines, U251MG, YKG-1, and U87, were used in this study. Cell proliferation was assessed by methyl thiazolyl tetrazorium (MTT) assays in the presence of EI236, in comparison to temozolomide (TMZ) and calmustine (BCNU), i.e. the clinical standard drugs for GBM. Apoptosis was analyzed by fluorescence activated cells sorting. In addition, we have examined whether EI236 inhibited the tumor growth with/without AMF application in animal models. Tumors were induced by implantation of U251MG cells into the hip of female Balb-c mice. Seven days after the implantation of GBM cells, EI236, BCNU or normal saline (control) was injected respectively into the tumors and mice were exposed to an AMF application(330.8A, 280kHz) for 30 minutes. Therefore, we calculated the tumor volume and the regression rate of tumors twice a week. Result: EI236 inhibited the proliferation of all cell lines and increased apoptosis in a dose dependent manner. Moreover, we found that EI236 had much greater anti-cancer effect than the clinical standard drugs. Mice bearing GBM cancer cells in their hip were then subjected to a double combination therapy, consisting of local injection of EI236 and hyperthermic treatment by AMF application. Tumor sizes in both drug stimulation groups were reduced, especially that in EI236 with AMF application group was highly reduced, while that in control group was increased. Conclusion: EI236 has greater anti-cancer effect than TMZ and BCNU, i.e. the clinical standard drugs. Besides this strong anti-cancer effect, EI236 has hyperthermic effect upon an AMF application because of heat generation. Accordingly, EI236 may enable us to develop novel strategies in GBM treatment, i.e. hyperthermic-chemotherapy with a single-drug compound. Note: This abstract was not presented at the meeting. Citation Format: Makoto Ohtake, Masanari Umemura, Itaru Sato, Kayoko Oda, Akane Nagasako, Ayako Makino, Haruki Aoyama, Mayumi Katsumata, Haruki Eguchi, Nobutaka Kawahara, Yoshihiro Ishikawa. Simultaneous hyperthermic-chemotherapy for glioblastoma using a single anti-cancer compound with intrinsic magnetism. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4548. doi:10.1158/1538-7445.AM2015-4548

A Smart Hyperthermia Nanofiber with Switchable Drug Release for Inducing Cancer Apoptosis

AbstractA smart hyperthermia nanofiber is described with simultaneous heat generation and drug release in response to ‘on‐off’ switching of alternating magnetic field (AMF) for induction of skin cancer apoptosis. The nanofiber is composed of a chemically‐crosslinkable temperature‐responsive polymer with an anticancer drug (doxorubicin; DOX) and magnetic nanoparticles (MNPs), which serve as a trigger of drug release and a source of heat, respectively. By chemical crosslinking, the nanofiber mesh shows switchable changes in the swelling ratio in response to alternating ‘on‐off’ switches of AMF because the self‐generated heat from the incorporated MNPs induces the deswelling of polymer networks in the nanofiber. Correspondingly, the ‘on‐off’ release of DOX from the nanofibers is observed in response to AMF. The 70% of human melanoma cells died in only 5 min application of AMF in the presence of the MNPs and DOX incorporated nanofibers by double effects of heat and drug. Taken together these advantages on both the nano‐ and macroscopic scale of nanofibers demonstrate that the dynamically and reversibly tunable structures have the potential to be utilized as a manipulative hyperthermia material as well as a switchable drug release platform by simple switching an AMF ‘on’ and ‘off’.

Lysosomal Membrane Permeabilization by Targeted Magnetic Nanoparticles in Alternating Magnetic Fields

Lysosomal death pathways are being explored as alternatives of overcoming cancer tumor resistance to traditional forms of treatment. Nanotechnologies that can selectively target and induce permeabilization of lysosomal compartments in cells could become powerful medical tools. Here we demonstrate that iron oxide magnetic nanoparticles (MNPs) targeted to the epidermal growth factor receptor (EGFR) can selectively induce lysosomal membrane permeabilization (LMP) in cancer cells overexpressing the EGFR under the action of an alternating magnetic field (AMF). LMP was observed to correlate with the production of reactive oxygen species (ROS) and a decrease in tumor cell viability. Confocal microscopy images showed an increase in the cytosolic activity of the lysosomal protease cathepsin B. These observations suggest the possibility of remotely triggering lysosomal death pathways in cancer cells through the administration of MNPs which target lysosomal internalization pathways and the application of AMFs.

Magnetocaloric effect in magnetothermally-responsive nanocarriers for hyperthermia-triggered drug release

The magnetocaloric effects and lower critical solution temperature (LCST) were investigated in a magnetothermally-responsive nanocarrier for magnetothermal drug release under alternating magnetic field (AMF). The Mn0.2Zn0.8Fe2O4 nanoparticles with low Tc were dispersed in a polymeric matrix consisting of N-Isopropyl acrylamide (NIPAAm) and N-hydroxymethyl acrylamide (HMAAm). The magnetocaloric effects and LCST of the nanocarriers were characterized by using high-resolution electron transmission microscopy, thermogravimetric analyses, and vibrating sample magnetometer. The maximum self-heating temperature of 42.9 °C was achieved by optimizing the Mn0.2Zn0.8Fe2O4 concentration in the polymer matrix. By adjusting the NIPAAm to HMAAm ratio, the LCST was controlled at an ideal level of 40.1 °C for efficient thermosensitive drug delivery. Magnetothermally responsive drug release of Doxorubicin, an anticancer drug, was significantly enhanced by application of an external AMF on the nanocarriers. The cytotoxicity experimental results in vitro show good biocompatibility and efficient therapeutic effects in cancer treatment.

Development of a highly efficient implanted thermal ablation device:in vivoexperiment in rat liver

To evaluate an implanted thermal ablation device that can be heated with high efficiency using a resonant circuit as the implant. 16 rats were used. The implants, adjusted at a resonance frequency of 4 MHz, were fixed on the surface of the liver of rats under laparotomy. In 14 of 16 rats, an alternating magnetic field (AMF) was applied for 6 min with an output of 300 W from outside the body using a ferrite core applicator. The implant temperature during AMF exposure was measured. The 14 rats were divided into 5 groups, depending on time from AMF application until they were sacrificed (1 h, 1 day, 3 days, 7 days and 1 month after application). Two rats not exposed to AMF were used as controls. Livers were removed and evaluated; the cross-sectional area and width of the ablated region were measured. During AMF exposure, the implant temperature rose to 127.8±39.3 °C (mean±standard deviation). The cross-sectional area of the ablated region was largest after 1 day and tended to decrease with time. The widths of the ablated region were 4.87±0.22 mm, 4.15±0.36 mm, 3.67±0.58 mm and 3.24±0.16 mm in the 1 day, 3 day, 7 day and 1 month groups, respectively. No significant differences (p<0.05) were seen in either cross-sectional area or width of the ablated region. Sufficient heat for ablation was obtained in vivo using a newly developed implanted thermal ablation device. This device may be a new option for thermal ablation therapy.

Preparation and characterization of temperature-responsive magnetic composite particles for multi-modal cancer therapy

The temperature-responsive magnetic composite particles were synthesized by emulsion-free polymerization of N-isopropylacrylamide (NIPAAm) and acrylamide (Am) in the presence of oleic acid-modified Fe(3)O(4) nanoparticles. The magnetic properties and heat generation ability of the composite particles were characterized. Furthermore, temperature and alternating magnetic field (AMF) triggered drug release behaviors of vitamin B(12)-loaded composite particles were also examined. It was found that composite particles enabled drug release to be controlled through temperature changes in the neighborhood of lower critical solution temperature. Continuous application of AMF resulted in an accelerated release of the loaded drug. On the other hand, intermittent AMF application to the composite particles resulted in an "on-off", stepwise release pattern. Longer release duration and larger overall release could be achieved by intermittent application of AMF as compared to continuous magnetic field. Such composite particles may be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release.

Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors.

Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 ± 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.

Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release

Hydrogel nanocomposites are novel macromolecular biomaterials that promise to impact various applications in medical and pharmaceutical fields. In this paper, magnetic nanocomposites of temperature responsive hydrogels were used to illustrate remote controlled (RC) drug delivery. A high frequency alternating magnetic field (AMF) was used to trigger the on-demand pulsatile drug release from the nanocomposites. Nanocomposites were synthesized by incorporation of superparamagnetic Fe 3O 4 particles in negative temperature sensitive poly ( N-isopropylacrylamide) hydrogels. Pulses of AMF were applied to the nanocomposites and the kinetics of collapse and recovery were characterized. Application of AMF resulted in uniform heating within the nanocomposites leading to accelerated collapse and squeezing out large amounts of imbibed drug (release at a faster rate). Remote controlled pulsatile drug release was characterized for different drugs as well as for different ON–OFF durations of the AMF.