Magnetic Field Stimulation Research Articles

Assessing Suitability of Co@Au Core/Shell Nanoparticle Geometry for Improved Theranostics in Colon Carcinoma.

The interactions between cells and nanomaterials at the nanoscale play a pivotal role in controlling cellular behavior and ample evidence links cell intercommunication to nanomaterial size. However, little is known about the effect of nanomaterial geometry on cell behavior. To elucidate this and to extend the application in cancer theranostics, we have engineered core–shell cobalt–gold nanoparticles with spherical (Co@Au NPs) and elliptical morphology (Co@Au NEs). Our results show that owing to superparamagnetism, Co@Au NPs can generate hyperthermia upon magnetic field stimulation. In contrast, due to the geometric difference, Co@Au NEs can be optically excited to generate hyperthermia upon photostimulation and elevate the medium temperature to 45 °C. Both nanomaterial geometries can be employed as prospective contrast agents; however, at identical concentration, Co@Au NPs exhibited 4-fold higher cytotoxicity to L929 fibroblasts as compared to Co@Au NEs, confirming the effect of nanomaterial geometry on cell fate. Furthermore, photostimulation-generated hyperthermia prompted detachment of anti-cancer drug, Methotrexate (MTX), from Co@Au NEs-MTX complex and which triggered 90% decrease in SW620 colon carcinoma cell viability, confirming their application in cancer theranostics. The geometry-based perturbation of cell fate can have a profound impact on our understanding of interactions at nano-bio interface which can be exploited for engineering materials with optimized geometries for superior theranostic applications.

Effect of Ascophyllum nodosum Alga Application on Microgreens, Yield, and Yield Components in Oats Avena sativa L.

This paper describes the influence of Ascophyllum nodosum algae on the seeds, microgreens, yield, and yield components of oat Avena sativa cv. Bingo. This article includes the results from three experiments. In one of the experiments, the oat seeds were soaked in a solution of demineralized water with dried comminuted and homogenized algae. For the FT–Raman spectra measurements, a spectrometer with an Nd:YAG laser, with a germanium detector, was used. The results obtained show that an excessively low as well as an excessively high alga concentration did not have an influence on the change in oat composition. Other algae concentrations that were used in these experiments caused significant chemical changes in the oat seeds. For the FT–Raman data, separation of the control from all the oat grains treated with different algae concentrations was possible. The aim of the pot experiment was to determine the effect of the application of algae (in different doses) on the A. sativa green mass of young plants (microgreens). The certified oat seeds, after being soaked in a solution with algae, were planted in the ground. For the chemometric analysis of the oat samples, a Fourier-transform infrared (FTIR) spectrometer device was used. The data were recorded with a viewing diamond with an attenuated total reflection (ATR) crystal plate. The FTIR spectra showed that soaking in an algae suspension affected the germination, general metabolism, and chemical composition of the oats. The use of algae did not change the lipid content of the plant. The three-year field experiment was established by introducing two factors: A. nodosum application (A) and a pre-sowing stimulation with a low-frequency magnetic field (S). The influence of experimental factors on the oat yield and its structure (yield structure components and yield components) was investigated. The beneficial effect of algae on oat yield was demonstrated by improved parameters such as the number and weight of the grains; however, under field conditions, the pre-sowing magnetic field stimulation of seeds did not have a beneficial effect. Various weather conditions also had a great influence on the yield. This study also considered the role of A. nodosum as a biostimulant in plants, and this showed potential under less favorable conditions.

Assessing the combination of magnetic field stimulation, iron oxide nanoparticles, and aligned electrospun fibers for promoting neurite outgrowth from dorsal root ganglia in vitro

Magnetic fiber composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and electrospun fibers have shown promise in tissue engineering fields. Controlled grafting of SPIONs to the fibers post-electrospinning generates biocompatible magnetic composites without altering desired fiber morphology. Here, for the first time, we assess the potential of SPION-grafted scaffolds combined with magnetic fields to promote neurite outgrowth by providing contact guidance from the aligned fibers and mechanical stimulation from the SPIONs in the magnetic field. Neurite outgrowth from primary rat dorsal root ganglia (DRG) was assessed from explants cultured on aligned control and SPION-grafted electrospun fibers as well as on non-grafted fibers with SPIONs dispersed in the culture media. To determine the optimal magnetic field stimulation to promote neurite outgrowth, we generated a static, alternating, and linearly moving magnet and simulated the magnetic flux density at different areas of the scaffold over time. The alternating magnetic field increased neurite length by 40% on control fibers compared to a static magnetic field. Additionally, stimulation with an alternating magnetic field resulted in a 30% increase in neurite length and 62% increase in neurite area on SPION-grafted fibers compared to DRG cultured on PLLA fibers with untethered SPIONs added to the culture media. These findings demonstrate that SPION-grafted fiber composites in combination with magnetic fields are more beneficial for stimulating neurite outgrowth on electrospun fibers than dispersed SPIONs. Statement of significanceAligned electrospun fibers improve axonal regeneration by acting as a passive guidance cue but do not actively interact with cells, while magnetic nanoparticles can be remotely manipulated to interact with neurons and elicit neurite outgrowth. Here, for the first time, we examine the combination of magnetic fields, magnetic nanoparticles, and aligned electrospun fibers to enhance neurite outgrowth. We show an alternating magnetic field alone increases neurite outgrowth on aligned electrospun fibers. However, combining the alternating field with magnetic nanoparticle-grafted fibers does not affect neurite outgrowth compared to control fibers but improves outgrowth compared to freely dispersed magnetic nanoparticles. This study provides the groundwork for utilizing magnetic electrospun fibers and magnetic fields as a method for promoting axonal growth.

Magnetic Field Stimulation Effect on Germination and Antioxidant Activities of Presown Hybrid Seeds of Sunflower and Its Seedlings

Magnetic field biostimulation plays a significant role in enhancing the germination of seeds and increasing the metabolic rate. The low magnetic field effect for long exposure time and its effect on antioxidant profiling have not been studied. Therefore, in the recent findings, the static magnetic field’s impact on sunflower seeds subjected to the magnetic field at varying intensity (millitesla) for different exposure times was examined. The effectiveness of magnetic biostimulation on presown sunflower seeds, growth parameters of seedlings (biomass, root and shoot length, fresh and dry weight of roots, shoots, leaf, and height of plants), and antioxidant activities were also studied. It has been revealed that magnetic treatment at 50 mT/45 min greatly influenced the growth parameters, including mean germination growth (100 ± 0.02) and final emergence rate. Concerning the antioxidant parameters, seed variety FH620 at 500 µg/µL concentration showed significant results compared to other varieties. FTIR was employed to determine the conformational changes and functional groups of organic compounds from sunflower seedlings. Tocopherol analysis by HPLC showed that magnetic treatment at 50 mT/45 min had a higher concentration of vitamin E compared to the control group. These modifications indicated that magnetic field induction enhanced seeds’ inner energy that led to seedlings’ growth and development enhancement. Besides, magnetic field pretreatment has been shown to have a beneficial influence on sunflower seeds and their bioactive compounds. Future studies should be focused on growth characteristics at the field level and yield attributes.

Transient Modulation of Working Memory Performance and Event-Related Potentials by Transcranial Static Magnetic Field Stimulation over the Dorsolateral Prefrontal Cortex

Transcranial static magnetic field stimulation (tSMS) can modulate human cortical excitability and behavior. To better understand the neuromodulatory effect of tSMS, this study investigates whether tSMS applied over the left dorsolateral prefrontal cortex (DLPFC) modulates working memory (WM) performance and its associated event-related potentials (ERPs). Thirteen healthy participants received tSMS or sham stimulation over the left DLPFC for 26 min on different days. The participants performed a 2-back version of the n-back task before, during (20 min after the start of stimulation), immediately after, and 15 min after the stimulation. We examine reaction time for correct responses, d-prime reflecting WM performance, and the N2 and P3 components of ERPs. Our results show that there was no effect of tSMS on reaction time. The d-prime was reduced, and the N2 latency was prolonged immediately after tSMS. These findings indicate that tSMS over the left DLPFC affects WM performance and its associated electrophysiological signals, which can be considered an important step toward a greater understanding of tSMS and its use in studies of higher-order cognitive processes.

Research on a Cell Proliferation Model Based on A549 Cell Line With Magnetic Field Stimulation

Mutation of the K-Ras gene has been widely found in non-small cell lung cancer. Compared with other mutations of lung cancer, the drugs cannot effectively target mutant K-Ras. However, the mitosis of cancer cells is vulnerable to external interference. Our previous study showed that electromagnetic fields (MFs) could suppress cell proliferation. In this article, a cell proliferation model based on the A549 cell line was established while considering the effects of MFs. In addition, the parameters of the A549 cell proliferation model were regressed by the finite difference method and verified by numerical simulation. Based on the calculations, the density of the A549 cells reflects the trend of measured data from optical microscopy. This approach not only helps reveal the mechanism of MFs on cancer cells but also suggests a new way to predict the effects of magnetic stimulation on cancer inhibition.

Pulsed high magnetic field-induced reversible blood-brain barrier permeability to enhance brain-targeted drug delivery

ABSTRACT The present study aimed to select an effective Pulsed High Magnetic Field (PHMF) stimulation protocol that would induce the Blood-Brain Barrier’s (BBB) reversible permeability to enhance brain-targeted drug delivery. PHMF was applied to the skull over the right hemisphere of 60 Wistar rats. The sham group contained other 10 rats that did not receive PHMF stimulation. The investigated parameters were repetition frequencies (0.25, 1, and 4 Hz as well as the effective low frequency combined with 10 Hz) and numbers of pulses in each train. Evans Blue Dye (EBD) uptake within the brain parenchyma was measured to select an effective PHMF stimulation protocol. BBB reversibility was evaluated by measuring EBD uptake and Gadobutrol retention, through MRI signal intensity enhancement, within brain parenchyma after exposure to the effective PHMF stimulation protocol at different time points including 0.5, 1, and 24 hours. The obtained results showed that the PHMF stimulation increased the BBB’s reversible permeability; this increase was more significant for 28 pulses with 1 Hz frequency (P < .0001). Changes in EBD uptake and MRI signal intensity in the exposed side (right hemisphere) peaked within 0.5–1 hour and returned to normal levels 24 hours after exposure to the effective protocol of PHMF stimulation (28 pulses with 1 Hz frequency). The Contrast-Enhanced MRI (CE-MRI) signal intensity confirmed the changes in EBD concentration. PHMF stimulation can be used as an effective protocol for enhancing the permeability reversibly of BBB, hence considered a potential clinical approach to brain-targeted drug delivery.

Magnetoresponsive nanozyme: magnetic stimulation on the nanozyme activity of iron oxide nanoparticles.

The iron oxide nanoparticles (IONPs) that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications. However, the effect of magnetic stimulation in fine-tuning the nanozyme activities remains unclear. Here, we have constructed a series of IONPs with different magneto-thermal conversion abilities, and systematically study the effect of magnetic field stimulation on the peroxidase (POD) activity of IONPs. The results show that POD activity is effectively amplified via an in situ alternating magnetic field (AMF) stimulation with no solution temperature rise, and the degree of activity enhancement is closely related to the magnetic heating ability of the IONPs, confirming the origin of activity enhancement arises from the local magnetothermal effect. As the first report to prove magnetothermal regulation on nanozyme activity and to shed lights on the underlying correlation between activity enhancement and the intrinsic specific absorption rate (SAR), this work is expected to provide important support for future design of new magnetoresponsive nanozymes in various practical applications.

Null Effect of Transcranial Static Magnetic Field Stimulation over the Dorsolateral Prefrontal Cortex on Behavioral Performance in a Go/NoGo Task.

The purpose of this pilot study was to investigate whether transcranial static magnetic field stimulation (tSMS), which can modulate cortical excitability, would influence inhibitory control function when applied over the dorsolateral prefrontal cortex (DLPFC). Young healthy adults (n = 8, mean age ± SD = 24.4 ± 4.1, six females) received the following stimulations for 30 min on different days: (1) tSMS over the left DLPFC, (2) tSMS over the right DLPFC, and (3) sham stimulation over either the left or right DLPFC. The participants performed a Go/NoGo task before, immediately after, and 10 min after the stimulation. They were instructed to extend the right wrist in response to target stimuli. We recorded the electromyogram from the right wrist extensor muscles and analyzed erroneous responses (false alarm and missed target detection) and reaction times. As a result, 50% of the participants made erroneous responses, and there were five erroneous responses in total (0.003%). A series of statistical analyses revealed that tSMS did not affect the reaction time. These preliminary findings suggest the possibility that tSMS over the DLPFC is incapable of modulating inhibitory control and/or that the cognitive load imposed in this study was insufficient to detect the effect.

In vivo local transcranial static magnetic field stimulation alters motor behavior in normal rats

Transcranial static magnetic field stimulation (tSMS) has inhibitory neuromodulatory effects on the human brain. Most of the studies on static magnetic fields have been performed in vitro. To further understand the biological mechanisms of tSMS, we investigated the effects of in vivo tSMS on motor behavior in normal awake rats. The skull of a male Wistar rat was exposed and a polyethylene tube was attached to the skull using dental cement at the center of the motor cortex (n = 7) or the other cortex (n = 6). By attaching a cylindrical NdFeB neodymium magnet into the tube, in vivo tSMS (REAL) was performed. For SHAM, we applied a similar size non-magnetic stainless-steel cylinder. All rats received twice each SHAM and REAL stimulation every two days using a crossover design, and motor function was measured during the stimulation. Activity level and asymmetry of forelimb use were not affected, but less accurate movements in the horizontal ladder test were found in REAL stimulation of the motor cortex. This study shows that in vivo tSMS has inhibitory neuromodulatory effects on motor behavior depending on the stimulated region on the rat cortex.

Detection of Surface Charge Enhancement in Magnetoelectric Nanoparticles Induced by AC Magnetic Field Stimulation using Single Entity Approach

Magneto-electric nanoparticles (MENPs), composed of a piezoelectric shell and a ferromagnetic core, exhibited enhanced cell uptake and controlled drug release due to the enhanced localized electric field (surface charge/potential) and the generation of acoustics, respectively, upon applying alternating current (AC) magnetic (B)-field stimulation. This research, for the first time, implements an electrochemical single-entity approach to probe AC B-field induced strain mediated surface potential enhancement on MENP surface. The surface potential changes at the single-NP level can be probed by the open circuit potential changes of the floating carbon nanoelectrode (CNE) during the MENP-CNE collision events. The results confirmed that the AC B-field (60 Oe) stimulation caused localized surface potential enhancement of MENP. This observation is associated with the presence of a piezoelectric shell, whereas magnetic nanoparticles were found unaffected under identical stimulation.

Effect of seed treatment by low-frequency electromagnetic field on soybean productivity

The development of science and technology introduces new approaches in plant breeding and various methods to increase plant productivity. One of the latest methods is the implementation of an environmentally friendly technique of using a pulsed low-frequency electromagnetic field (PEMP). The paper presents the results of the influence of the electromagnetic stimulation of soybean seeds on grain weight per plant, weight of 1,000 grains and grain yield in different agroecological conditions. In the three-year research, in the period from 2013 to 2015, the soybean variety Valjevka was used, grown with different amounts of fertilizers (control - without fertilization, 750 kg/ha and 1300 kg/ha). Before sowing, the seed was subjected to PEMP stimulation in variants: control - without stimulation and alternating magnetic field stimulation (PEMP) with induction of 30 mT and exposure time of 15 minutes. The average grain weight per plant during seed stimulation was 11.53% (12.09) higher than without PEMP (10.84). The weight of 1,000 grains with PEMP was 155.99 g, which was 2.06% higher than the weight of 1,000 grains of the variant without PEMP (152.83 g). The average soybean grain yield for all three years of research with seed stimulation was 4.85% higher (3,481.25 kg/ha) than without PEMP (3,320.14 kg/ha). Stimulation of seeds with PEMP has economic justification given the growth of soybean prices on the world stock market. The results show that the PEMP treatment of soybean seeds can significantly affect soybean grain yield and counteract side effects such as drought and lack of fertilizers.

Frequency Effect on Proliferation of Human Liver Cancer Cells under Alternating Magnetic Field

The effects of alternating magnetic field (AMF) stimulation on the proliferation of human liver cancer cells (HepG2) under varying frequencies from 500 ㎐ to 2 ㎑ were investigated. The AMF stimulator generated a magnetic field of 5 mT with a saw tooth pulse waveform, the frequency of alternating pulses was controlled by the duty factor of the digital control circuit. HepG2 cells were cultured in a 6-well plate over a magnetic coil using a cooling system while been kept for 48 hours in an incubator. After magnetic stimulation of 0.5, 1 and 2 ㎑, the proliferation rates of the HepG2 cells saw almost no difference compared to liver cancer cells that were not stimulated. However, the proliferation rates at 1.4 ㎑ were reduced by up to 66 % compared to the non-stimulated cells. In other words, HepG2 cancer cells can be suppressed by magnetic stimulation of a certain frequency. These results are in good agreement with those from analysis of cell viability using MTT assay, a colorimetric assay used for assessing cell metabolic activity. This phenomenon of a suppression frequency may be related with various ionic flows that occur in the ion channels of cell membranes.

Effect of Pulsed Magnetic Field Stimulation of Bio-Conductance Response on The Human Meridian Circulatory System

Effect of Pulsed Magnetic Field Stimulation of Bio-Conductance Response on The Human Meridian Circulatory System

Influence of Static Magnetic Field Stimulation on the Accuracy of Tachystoscopically Presented Line Bisection.

Transcranial static magnetic stimulation (tSMS) has been known to reduce human cortical excitability. Here, we investigated whether tSMS would modulate visuo-spatial cognition in healthy humans. Subjects performed a visuo-spatial task requiring judgements about the symmetry of pre-bisected lines. Visual stimuli consisted of symmetrically or asymmetrically transected lines, tachystoscopically presented for 150 ms on a computer monitor. Task performance was examined before, immediately after, and 10 min after tSMS/sham stimulation of 20 min over the posterior parietal cortex (PPC: P4 from the international 10–20 system) or superior temporal gyrus (STG: C6). Nine out of 16 subjects misjudged pre-bisected lines by consistently underestimating the length of the right-side segment (judging lines to be exactly pre-bisected when the transector was located to the left of the midpoint, or judging the left-side segment to be longer when the transector was located at the midpoint). In these subjects showing a leftward bias, tSMS over the right STG reduced the magnitude of the leftward bias. This did not occur with tSMS over the right PPC or sham stimulation. In the remaining right-biased subjects, no intervention effect was observed with any stimulation. Our findings indicate that application of tSMS over the right STG modulates visuo-spatial cognition in healthy adults.

Lanthanide-Activated Nanoparticles: A Toolbox for Bioimaging, Therapeutics, and Neuromodulation.

Owing to their unique features, the past decade has witnessed rapid developments of lanthanide-activated nanoparticles for biological applications. These include highly tunable upconverting and downshifting photoluminescence when illuminated in deep tissue, excellent photostability against blinking and bleaching effects, biocompatibility through versatile surface modification, and ease of achieving multifunctionality, as well as satisfactory signal output. These attributes make lanthanide-doped nanoparticles an ideal toolbox for advanced bioimaging and next-generation therapeutics.The interest in lanthanide-doped nanoparticles for biomedical research arises from their unique optical properties in response to deep-tissue-penetrable light sources. Upon near-infrared irradiation, these nanoparticles with properly doped emitters display photon upconversion with large anti-Stokes shifts and broad-spectrum tunability from the ultraviolet to the visible. It is also possible to achieve orthogonal photoluminescence with variations in wavelength and lifetime. Coupled with surface ligands, dyes, biomolecules, or other types of functional nanomaterials, lanthanide-doped nanoparticles offer new opportunities for applications in bioimaging, advanced oncotherapy, and neuromodulation. Given the possibility of locating downshifting luminescence at "biological transmission windows", exquisite design of lanthanide-doped nanoparticles also enables deep-tissue imaging with high spatial resolution. In addition, these nanoparticles can respond to high-energy photons, such as X-rays, to trigger nonradioactive and radiative pathways, making it possible to develop high-sensitivity X-ray detectors. Precise control of paramagnetic lanthanide ions in nanocrystal lattices also provides advanced materials for high-performance magnetic resonance imaging in medical diagnostics and biomedical research. Full consideration of fundamental attributes of lanthanide-doped nanoparticles will facilitate the design of multifunctional and sensitive probes and improve diagnostic and therapeutic outcomes.In this Account, we categorize various lanthanide-activation strategies into three modes: near-infrared excitation, X-ray irradiation, and magnetic field stimulation. We introduce energy manipulations in upconverting, downshifting, and persistence luminescence in spectral and time domains and discuss how they can be applied in biological practices. We assess general design principles for lanthanide-activated nanosystems with multiple modalities of bioimaging, oncotherapy, and neuromodulation. We also review the current state-of-the-art in the field of lanthanide-based theranostic nanoplatforms, with particular emphasis on energy conversion and nano-/biointerfacing as well as emerging bioapplications. In this context, we also highlight recent advances in controlling optical properties of nanoplatforms for single- or multimodal bioimaging, stimulus-responsive phototherapy, and optogenetics. Finally, we discuss future opportunities and challenges of this exciting research field.

Low frequency vortex magnetic field reduces amyloid β aggregation, increase cell viability and protect from amyloid β toxicity

ABSTRACT Plaques formed by abnormal accumulation of amyloid β-peptide (Aβ) lead to onset of Alzheimer’s disease (AD). Pharmacological treatments do not reduce Aβ aggregation neither restore learning and memory. Noninvasive techniques have emerged as an alternative to treat AD, such as stimulation with electromagnetic fields (EMF) that decrease Aβ deposition and reverses cognitive impairment in AD mice, even though some studies showed side effects on parallel magnetic fields stimulation. As a new approach of magnetic field (MF) stimulation, vortex magnetic fields (VMF) have been tested inducing a random movement of charged biomolecules in cells, promoting cell viability and apparently safer than parallel magnetic fields. In this study we demonstrate the effect of VMF on Aβ aggregation. The experimental strategy includes, i) design and construction of a coil capable to induce VMF, ii) evaluation of VMF stimulation on Aβ peptide induced-fibrils-formation, iii) evaluation of VMF stimulation on SH-SY5Y neuroblastoma cell line in the presence of Aβ peptide. We demonstrated for the first time that Aβ aggregation exposed to VMF during 24 h decreased ~ 86% of Aβ fibril formation compared to control. Likewise, VMF stimulation reduced Aβ fibrils-cytotoxicity and increase SH-SY5Y cell viability. These data establish the basis for future investigation that involve VMF as inhibitor of Aβ-pathology and indicate the therapeutic potential of VMF for AD treatment.

Effects of magnetic fields on electricity generation in a photosynthetic ceramic microbial fuel cell

The aim of this study was to improve the efficiency of traditional proton exchange membranes by replacement using ceramic membranes with microalgae cathodes under various magnetic fields (MFs) of 100–300 mT in a ceramic microbial fuel cell (CMFC). The experimental results showed that the power generation can be enhanced by 61% when implementing a 200 mT MF. The application of a higher MF intensity, up to 200 mT, increased the electric charge generation yet decreased it with a higher MF value. Additionally, the MF had the ability to improve the power density of the CMFC, and a maximum power density of 35.9 mW m−2 and maximum current density of 158.7 mA m−2 were achieved with the 200 mT MF. Moreover, biocathode maintains a stable pH value that obtained more microalgae biomass by 200 mT MF stimulation. Further work will be focused on optimizing the appropriate MF intensity along with the capacity of carbon dioxide (CO2) absorption by microalgae in CMFC.

Antiinterference Function of Scale-Free Spiking Neural Network Under AC Magnetic Field Stimulation

The complexity and changeability of electromagnetic environment make the deficiency of traditional methods of electromagnetic protection increasingly prominent. The organisms with the regulation of nervous system have advantages of self-adaptive, self-organizing, and self-repairing. Therefore, it is necessary to explore a new thought on electromagnetic protection by drawing from the biological self-adaptive advantage. In this study, two kinds of scale-free spiking neural networks (sfSNNs) with different clustering coefficients are constructed. Then, the antiinterference function of the sfSNNs under the ac magnetic field stimulation is evaluated and compared. Finally, the antiinterference mechanism is analyzed. The experimental results show that both sfSNNs have a certain antiinterference function, and the performance of the sfSNN with high clustering coefficient is better than that with low clustering coefficient in the antiinterference function; the dynamic evolution of neural information processing in the sfSNN is clarified; and the dynamic regulation of synaptic plasticity is the intrinsic factor of the antiinterference function of the sfSNNs. This study lays a theoretical foundation for the electromagnetic protection of electronic system based on adaptive bionic mechanism.

Targeted Osmotic Lysis of Highly Invasive Breast Carcinomas Using Pulsed Magnetic Field Stimulation of Voltage-Gated Sodium Channels and Pharmacological Blockade of Sodium Pumps.

Concurrent activation of voltage-gated sodium channels (VGSCs) and blockade of Na+ pumps causes a targeted osmotic lysis (TOL) of carcinomas that over-express the VGSCs. Unfortunately, electrical current bypasses tumors or tumor sections because of the variable resistance of the extracellular microenvironment. This study assesses pulsed magnetic fields (PMFs) as a potential source for activating VGSCs to initiate TOL in vitro and in vivo as PMFs are unaffected by nonconductive tissues. In vitro, PMFs (0–80 mT, 10 msec pulses, 15 pps for 10 min) combined with digoxin-lysed (500 nM) MDA-MB-231 breast cancer cells stimulus-dependently. Untreated, stimulation-only, and digoxin-only control cells did not lyse. MCF-10a normal breast cells were also unaffected. MDA-MB-231 cells did not lyse in a Na+-free buffer. In vivo, 30 min of PMF stimulation of MDA-MB-231 xenografts in J/Nu mice or 4T1 homografts in BALB/c mice, concurrently treated with 7 mg/kg digoxin reduced tumor size by 60–100%. Kidney, spleen, skin and muscle from these animals were unaffected. Stimulation-only and digoxin-only controls were similar to untreated tumors. BALB/C mice with 4T1 homografts survived significantly longer than mice in the three control groups. The data presented is evidence that the PMFs to activate VGSCs in TOL provide sufficient energy to lyse highly malignant cells in vitro and to reduce tumor growth of highly malignant grafts and improve host survival in vivo, thus supporting targeted osmotic lysis of cancer as a possible method for treating late-stage carcinomas without compromising noncancerous tissues.