Magnetoelectric Nanoparticles Research Articles

Physical Origin of Magnetoelectroporation

Magnetoelectroporation is an effective method of opening nanopores in cell membranes using magnetoelectric nanoparticles (MENPs) for the purpose of in vivo and in vitro delivery of drug substances to cancer cells. A microscopic approach is proposed as theoretical basis for that phenomenon. The underlying Hamiltonian includes the magnetic and ferroelectric subsystems characterized by two‐order parameters. The related magnetoelectric coefficient αHE characterizes the relationship between the applied magnetic field and a generated local electric field. Whereas the spontaneous polarization of the MENP is due to the arrangement of electric dipoles, there appears an additional spin‐assisted polarization owing to the magnetic phase transition. It is shown that the main contribution to the local field comes from . Moreover, the local electric field depends on the orientation of the easy‐axis magnetization of the MENPs with respect to applied external magnetic field. The magnetoelectric coefficient exhibits a nonlinear dependence on the external magnetic field. The results are based on an analytical Green's function method. The numerical calculations are performed for spherical, structurally heterogeneous nanoparticles composed on a core and a shell, where the noninteracting nanoparticles have the same diameter of 25 nm. The results are in qualitative agreement with experimental observations.

A proof-of-concept neurostimulation study with magneto-electric nanoparticles in organotypic human brain slice

A proof-of-concept neurostimulation study with magneto-electric nanoparticles in organotypic human brain slice

Core–Shell Magnetoelectric Nanoparticles: Materials, Synthesis, Magnetoelectricity, and Applications

Nanoparticles with small diameters and large surface areas have potential advantages and are actively utilized in various fields related to biomedical and catalytic applications. Multifunctional applications can be achieved by endowing nanoparticles with piezoelectric, quantum dot, magnetothermal, and piezoluminescent properties. In particular, multiferroic magnetoelectric nanoparticles (MENPs) can generate electricity by coupling piezoelectric and magnetostrictive properties when an external magnetic field, which is harmless to the human body, is applied. In this regard, magnetoelectricity (ME) induced by a magnetic field makes MENPs useful for various biomedical and electrocatalytic applications. The ME voltage coefficients, which express the efficiency of energy conversion from magnetic field to electricity, show differences depending on the setup for ME measurements of MENPs. Therefore, numerous attempts have been made to optimize the ME characterization method to reduce measurement errors resulting from charge leakages caused by the specimen preparation, as well as to investigate the ME effect of a single nanoparticle. Our review is focused on the structures, syntheses (hydrothermal and sol–gel methods), activation mechanism, and measurement of magnetoelectricity, as well as applications, of core–shell MENPs.

Magnetic-field-synchronized wireless modulation of neural activity by magnetoelectric nanoparticles

The in vitro study demonstrates wirelessly controlled modulation of neural activity using magnetoelectric nanoparticles (MENPs), synchronized to magnetic field application with a sub-25-msec temporal response. Herein, MENPs are sub-30-nm CoFe2O4@BaTiO3 core-shell nanostructures. MENPs were added to E18 rat hippocampal cell cultures (0.5 μg of MENPs per 100,000 neurons) tagged with fluorescent Ca2+ sensitive indicator cal520. MENPs were shown to wirelessly induce calcium transients which were synchronized with application of 1200-Oe bipolar 25-msec magnetic pulses at a rate of 20 pulses/sec. The observed calcium transients were similar, in shape and magnitude, to those generated through the control electric field stimulation with a 50-μA current, and they were inhibited by the sodium channel blocker tetrodotoxin. The observed MENP-based magnetic excitation of neural activity is in agreement with the non-linear M − H hysteresis loop of the MENPs, wherein the MENPs’ coercivity value sets the threshold for the externally applied magnetic field.

Modelling of magnetoelectric nanoparticles for non-invasive brain stimulation: a computational study

Objective. Recently developed magnetoelectric nanoparticles (MENPs) provide a potential tool to enable different biomedical applications. They could be used to overcome the intrinsic constraints posed by traditional neurostimulation techniques, namely the invasiveness of electrodes-based techniques, the limited spatial resolution, and the scarce efficiency of magnetic stimulation. Approach. By using computational electromagnetic techniques, we modelled the behaviour of recently designed biocompatible MENPs injected, in the shape of clusters, in specific cortical targets of a highly detailed anatomical head model. The distributions and the tissue penetration of the electric fields induced by MENPs clusters in each tissue will be compared to the distributions induced by traditional transcranial magnetic stimulation (TMS) coils for non-invasive brain stimulation positioned on the left prefrontal cortex (PFC) of a highly detailed anatomical head model. Main results. MENPs clusters can induce highly focused electric fields with amplitude close to the neural activation threshold in all the brain tissues of interest for the treatment of most neuropsychiatric disorders. Conversely, TMS coils can induce electric fields of several tens of V m−1 over a broad volume of the PFC, but they are unlikely able to efficiently stimulate even small volumes of subcortical and deep tissues. Significance. Our numerical results suggest that the use of MENPs for brain stimulation may potentially led to a future pinpoint treatment of neuropshychiatric disorders, in which an impairment of electric activity of specific cortical and subcortical tissues and networks has been assumed to play a crucial role.

Modeling of core-shell magneto-electric nanoparticles for biomedical applications: Effect of composition, dimension, and magnetic field features on magnetoelectric response.

The recent development of core-shell nanoparticles which combine strain coupled magnetostrictive and piezoelectric phases, has attracted a lot of attention due to their ability to yield strong magnetoelectric effect even at room temperature, thus making them a promising tool to enable biomedical applications. To fully exploit their potentialities and to adapt their use to in vivo applications, this study analyzes, through a numerical approach, their magnetoelectric behavior, shortly quantified by the magnetoelectric coupling coefficient (αME), thus providing an important milestone for the characterization of the magnetoelectric effect at the nanoscale. In view of recent evidence showing that αME is strongly affected by both the applied magnetic field DC bias and AC frequency, this study implements a nonlinear model, based on magnetic hysteresis, to describe the responses of two different core-shell nanoparticles to various magnetic field excitation stimuli. The proposed model is also used to evaluate to which extent realistic variables such as core diameter and shell thickness affect the electric output. Results prove that αME of 80 nm cobalt ferrite-barium titanate (CFO-BTO) nanoparticles with a 60:40 ratio is equal to about 0.28 V/cm∙Oe corresponding to electric fields up to about 1000 V/cm when a strong DC bias is applied. However, the same electric output can be obtained even in absence of DC field with very low AC fields, by exploiting the hysteretic characteristics of the same composites. The analysis of core and shell dimension is as such to indicate that, to maximize αME, larger core diameter and thinner shell nanoparticles should be preferred. These results, taken together, suggest that it is possible to tune magnetoelectric nanoparticles electric responses by controlling their composition and their size, thus opening the opportunity to adapt their structure on the specific application to pursue.

Nanomedicine and nanobiotechnology applications of magnetoelectric nanoparticles.

Unlike any other nanoparticles known to date, magnetoelectric nanoparticles (MENPs) can generate relatively strong electric fields locally via the application of magnetic fields and, vice versa, have their magnetization change in response to an electric field from the microenvironment. Hence, MENPs can serve as a wireless two-way interface between man-made devices and physiological systems at the molecular level. With the recent development of room-temperature biocompatible MENPs, a number of novel potential medical applications have emerged. These applications include wireless brain stimulation and mapping/recording of neural activity in real-time, targeted delivery across the blood-brain barrier (BBB), tissue regeneration, high-specificity cancer cures, molecular-level rapid diagnostics, and others. Several independent in vivo studies, using mice and nonhuman primates models, demonstrated the capability to deliver MENPs in the brain across the BBB via intravenous injection or, alternatively, bypassing the BBB via intranasal inhalation of the nanoparticles. Wireless deep brain stimulation with MENPs was demonstrated both in vitro and in vivo in different rodents models by several independent groups. High-specificity cancer treatment methods as well as tissue regeneration approaches with MENPs were proposed and demonstrated in in vitro models. A number of in vitro and in vivo studies were dedicated to understand the underlying mechanisms of MENPs-based high-specificity targeted drug delivery via application of d.c. and a.c. magnetic fields. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Multifunctional MEN-Doped Adhesives: Strengthening, Bond Quality Evaluation, and Variations in Magnetic Signal with Environmental Exposure

Adhesive bonding of polymer matrix composites offers various advantages over traditional fasteners, such as a uniform stress state, reduced weight, and delay of composite delamination. However, adhesive bonding has limited implementation due to challenges in the prediction of durability. This work introduces a new method to monitor an adhesively bonded composite joint by dispersing magneto-electric nanoparticles (MENs) into the polymer precursor and monitoring changes in their surface charge density by evaluating the output magnetic signal under an applied magnetic field. Real-time monitoring of the curing process of a polymer adhesive was performed and corroborated via thermal analysis and mechanical testing. Lap shear and end notch flexure testing showed that adding 1 vol% MENs led to a ~23% increase in shear strength and a ~12% increase in mode II critical energy release rates compared to the undoped adhesive. Adding 5 vol% MENs also increased the adhesive’s peak tensile stress by ~8%. Strengthening mechanisms of the doped adhesive were monitored using in situ electron microscopy. A correlation between water ingression and a change in the magnetic moment was observed. Results show the MENs’ potential as a structural health-monitoring tool for a wide range of materials and applications.

In silico assessment of electrophysiological neuronal recordings mediated by magnetoelectric nanoparticles

Magnetoelectric materials hold untapped potential to revolutionize biomedical technologies. Sensing of biophysical processes in the brain is a particularly attractive application, with the prospect of using magnetoelectric nanoparticles (MENPs) as injectable agents for rapid brain-wide modulation and recording. Recent studies have demonstrated wireless brain stimulation in vivo using MENPs synthesized from cobalt ferrite (CFO) cores coated with piezoelectric barium titanate (BTO) shells. CFO–BTO core–shell MENPs have a relatively high magnetoelectric coefficient and have been proposed for direct magnetic particle imaging (MPI) of brain electrophysiology. However, the feasibility of acquiring such readouts has not been demonstrated or methodically quantified. Here we present the results of implementing a strain-based finite element magnetoelectric model of CFO–BTO core–shell MENPs and apply the model to quantify magnetization in response to neural electric fields. We use the model to determine optimal MENPs-mediated electrophysiological readouts both at the single neuron level and for MENPs diffusing in bulk neural tissue for in vivo scenarios. Our results lay the groundwork for MENP recording of electrophysiological signals and provide a broad analytical infrastructure to validate MENPs for biomedical applications.

Exploring magneto-electric nanoparticles (MENPs): a platform for implanted deep brain stimulation

Exploring magneto-electric nanoparticles (MENPs): a platform for implanted deep brain stimulation

Where do we stand now regarding treatment of psychiatric and neurodegenerative disorders? Considerations in using magnetoelectric nanoparticles as an innovative approach.

Almost 1000 million people have recently been diagnosed with a mental health or substance disorder (Ritchie & Roser,2018). Psychiatric disorders, and their treatment, represent a big burden to the society worldwide, causing about 8 million deaths per year (Walker et al.,2015). Daily progress in science enables continuous advances in methods to treat patients; however, the brain remains to be the most unknown and complex organ of the body. There is a growing demand for innovative approaches to treat psychiatric as well as neurodegenerative disorders, disorders with unknown curability, and treatments mostly designed to slow disease progression. Based on that need and the peculiarity of the central nervous system, in the present review, we highlight the handicaps of the existing approaches as well as discuss the potential of the recently introduced magnetoelectric nanoparticles (MENPs) to become a game-changing tool in future applications for the treatment of brain alterations. Unlike other stimulation approaches, MENPs have the potential to enable a wirelessly controlled stimulation at a single-neuron level without requiring genetic modification of the neural tissue and no toxicity has yet been reported. Their potential as a new tool for targeting the brain is discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Neurological Disease.

Structure, magnetoelectric, and anticancer activities of core-shell Co0·8Mn0.2R0.02Fe1·98O4@BaTiO3 nanocomposites (R = Ce, Eu, Tb, Tm, or Gd)

In the present study, Co0·8Mn0.2R0.02Fe1·98O4 (CoMnRFe) (R = Ce, Eu, Tb, Tm, or Gd) nanoparticles (NPs) have been prepared and coated with BaTiO3 (BTO) using sonochemical and sol-gel methods to form various core-shell CoMnRFe@BTO magnetoelectric nanoparticles (MENs). The structure and morphologies of CoMnRFe@BTO MENs were assessed by XRD, SEM, TEM, HRTEM, EDX, XPS, and zeta potential techniques. The formation of core-shell CoMnRFe@BTO MENs was approved by XRD and HRTEM. SEM analysis of core-shell MENs revealed aggregation of spherical grains. The impact of CoMnRFe NPs and CoMnRFe@BTO MENs on human colon cancer cells (HCT-116) were examined and compared to normal non-cancerous cells (HEK-293) by using MTT assay and DAPI staining. After 48 h of treatment, it was found that CoMnRFe NPs showed a significant inhibitory effect on HCT-116 cells. Also, HEK-293 cells showed inhibitory action, but the percentage of cells viability was higher than HCT-116 cells. When HCT-116 cells are treated with CoMnRFe@BTO MENs, it showed a better cytotoxic effect compared to HEK-293 cells. In addition, CoMnRFe NPs and CoMnRFe@BTO MENs induced apoptotic cell death as revealed by DAPI staining. Our results suggest that CoMnRFe NPs and CoMnRFe@BTO MENs possess anti-colon cancer capabilities, but CoMnRFe@BTO MENs are safe materials as they do not cause any significant cytotoxic effect on HEK-293 cells compared to CoMnRFe NPs.

Modeling of adsorption and release kinetics of methotrexate from thermo/magnetic responsive CoFe2O4–BaTiO3, CoFe2O4–Bi4Ti3O12 and Fe3O4–BaTiO3 core-shell magnetoelectric nanoparticles functionalized with PNIPAm

From a pharmaceutical point of view, due to their magnetic and electric properties, novel magnetoelectric core-shell nanoparticles are a promising drug nanocarrier that will improve the efficiency of several therapies through the selective permeation of drugs on a specific cell population based on their cell membrane potential. The performances of previously synthesized CoFe2O4–BaTiO3, CoFe2O4–Bi4Ti3O12 and Fe3O4–BaTiO3 core-shell type magnetoelectric nanoparticles functionalized with PNIPAm were evaluated as potential drug nanocarriers by adsorption and release kinetics studies with methotrexate as model drug. Mathematical modeling allowed the comprehension of the overall phenomena affecting drug adsorption and release kinetics. In both cases, the physicochemical parameters and the underlying thermodynamic assumptions associated with models provided an insight into adsorption and release mechanisms, surface properties, and affinity degree. According to the kinetics adsorption studies the methotrexate adsorption was limited by the accessibility to surface at interparticle sites. Additionally, “L” type adsorption isotherms indicated multiple layer formation, the cooperative adsorption of methotrexate molecules and their homogenous surface distribution. Freundlich model was the best describing methotrexate adsorption phenomenon.Special focus was given to nanoparticles stability on dispersion effects over adsorption efficiency by submitting or not the nanoparticles to 1-min initial sonication at the beginning of adsorption process, affording important mechanistic insights. The maximum methotrexate adsorption was achieved at concentrations near the saturation submitted to sonication.Thereupon, the subsequent consequences of changes of surface area during methotrexate adsorption was observed in release profiles. Fascinating release profiles were observed from MENs submitted to different conditions of temperature, (25 or 40 °C), methotrexate loaded amount, and the application of a magnetic field due to surface area fluctuations during methotrexate adsorption. Rregardless their composition, the nanoparticles shown the same physicochemical behavior, manifested as comparable drug release profiles. The nanoparticles demonstrated sensibility to both, temperature and alternating magnetic fields stimuli, nevertheless the overall drug release was achieved only under the effects of magnetic stimulus. Methotrexate interparticle-localized resulted in an incomplete release at temperatures below and above PNIPAm lowest critical solution temperature. In summary, these nanocarriers shown a good in vitro performance, so a suitable in vivo behavior is expected.

Magnetoelectric Nanoparticles: Evaluating Stimulation Feasibility of the Possible Next Generation Approach for Deep Brain Stimulation

The purpose of this study is to quantify the distributions of the electric field induced by CoFe <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> core - BaTiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> shell magneto-electric nanoparticles (MENPs) when localized in deep brain structures. These fields can be used for deep brain stimulation (DBS), and their effect is compared to the fields induced by conventional DBS electrodes in monopolar and bipolar configuration. A computational approach based on finite element method was applied, along with the use of a highly detailed anatomical model of the brain structures. Different MENPs configurations were investigated and compared to conventional DBS electrode configuration. The activation of nervous fibers was quantified by calculating the Activation Function (AF) defined as the second derivative of the electric potential along the fiber. Electric field amplitudes obtained by MENPs were much lower than the ones obtained by the monopolar and bipolar electrode configurations. The AF values showed that MENPs were able to obtain very localized activation patterns along the fibers. In addition to the minimal invasiveness and proven biocompatibility of the MENPs, the results show that the proposed approach represents an important step towards a selective and minimally invasive strategy for DBS. All these findings are essential in identifying the unique characteristics that MENPs could provide for nervous system stimulation, and how the use of MENPs could improve the development of a new generation of DBS techniques.

Drug Response Prediction of Liver Cancer Cell Line Using Deep Learning

Cancer is the second deadliest human disease worldwide with high mortality rate. Rehabilitation and treatment of this disease requires precise and automatic assessment of effective drug response and control system. Prediction of treated and untreated cancerous cell line is one of the most challenging problems for precise and targeted drug delivery and response. A novel approach is proposed for prediction of drug treated and untreated cancer cell line automatically by employing modified Deep neural networks. Human hepatocellular carcinoma (HepG2) cells are exposed to anticancer drug functionalized CFO@BTO nanoparticles developed by our lab. Prediction models are developed by modifying ResNet101 and exploiting the transfer learning concept. Last three layers of ResNet101 are re-trained for the identification of drug treated cancer cells. Transfer learning approach in an appropriate choice especially when there is limited amount of annotated data. The proposed technique is validated on acquired 203 fluorescent microscopy images of human HepG2 cells treated with drug functionalized cobalt ferrite@barium titanate (CFO@BTO) magnetoelectric nanoparticles in vitro. The developed approach achieved high prediction with accuracy of 97.5% and sensitivity of 100% and outperformed other approaches. The high performance reveals the effectiveness of the approach. It is scalable and fully automatic prediction approach which can be extended for other similar cell diseases such as lung, brain tumor and breast cancer.

Wireless deep brain stimulation in freely moving mice with nonresonant powering of magnetoelectric nanoparticles

Wireless deep brain stimulation in freely moving mice with nonresonant powering of magnetoelectric nanoparticles

Reactive helicity and reactive power in nanoscale optics: Evanescent waves. Kerker conditions. Optical theorems and reactive dichroism

Considering time-harmonic optical fields, we put forward the complex helicity and its alternating flow, together with their conservation equation: the complex helicity theorem. Its imaginary part constitutes a novel law that rules the build-up of what we establish as the reactive helicity through its zero time-average flow. Its associated reactive flow and the imaginary Poynting momentum that accounts for the accretion of reactive power are illustrated in two paradigmatic systems: evanescent waves and fields scattered from magnetodielectric dipolar nanoparticles. As for the former, we show that its reactive helicity may be experimentally observed as we introduce a reactive spin momentum and a reactive orbital momentum in terms of which we express the imaginary field momentum, whose transversal component produces an optical force on a magnetoelectric particle that, as we illustrate, may surpass and can be discriminated from the known force due to the so-called extraordinary momentum. We also uncover a nonconservative force on such a magnetoelectric particle, acting in the decay direction of the evanescent wave, and that may also be discriminated from the standard gradient force; thus making the reactive power of the wavefield also observable. Concerning the light scattered by magnetoelectric nanoparticles, we establish two optical theorems that govern the accretion of reactive helicity and reactive power on extinction of incident wave helicity and energy. Like a nule total, i.e., internal plus external, reactive power is at the root of a resonant scattered power, we show that a zero total reactive helicity underlies a resonant scattered helicity. These reactive quantities are shown to yield a novel interpretation of the two Kerker conditions, which we demonstrate to be linked to an absence, or minimum, of the overall scattered reactive energy. Further, we demonstrate that the first Kerker condition, under which the particle becomes dual on illumination with circularly polarized light, amounts to a nule overall scattered reactive helicity. Therefore these two reactive quantities are shown to underly the directivity of the particle scattering and emission. In addition, we discover a discriminatory property of the reactive helicity of chiral light incident on a chiral nanoparticle by excitation of the external reactive power. This should be useful for optical near field enantiomeric separation, an effect that we call reactive dichroism.

Magnetically controlled crystallographic properties of graphite sheets with self-assembled periodic arrays of magnetoelectric nanoparticles

This paper presents an experimental study in which 30-nm CoFe2O4–BaTiO3 core–shell magnetoelectric nanostructures (MENs) were embedded into graphite sheets to enable external control of intrinsic properties such as the intercalation process. The embedded nanoparticles were self-assembled into a honeycomb pattern with a characteristic period on the order of 200 nm, as confirmed through energy-dispersive spectroscopy (EDS) by scanning electron microscopy (SEM) as well as through atomic and magnetic force microscopy (AFM and MFM). Integration of the nanoparticles into the graphite structure was also confirmed through Fourier transform infrared (FT-IR) imaging and X-Ray diffraction (XRD) analysis. XRD measurements indicate crystallographic changes in the response to application of a 500-Oe magnetic field. M-H measurements by vibrating sample magnetometer (VSM) showed the coercivity of the nanoparticles on the order of 250 Oe.

Permeation Challenges of Drugs for Treatment of Neurological Tuberculosis and HIV and the Application of Magneto-Electric Nanoparticle Drug Delivery Systems.

The anatomical structure of the brain at the blood–brain barrier (BBB) creates a limitation for the movement of drugs into the central nervous system (CNS). Drug delivery facilitated by magneto-electric nanoparticles (MENs) is a relatively new non-invasive approach for the delivery of drugs into the CNS. These nanoparticles (NPs) can create localized transient changes in the permeability of the cells of the BBB by inducing electroporation. MENs can be applied to deliver antiretrovirals and antibiotics towards the treatment of human immunodeficiency virus (HIV) and tuberculosis (TB) infections in the CNS. This review focuses on the drug permeation challenges and reviews the application of MENs for drug delivery for these diseases. We conclude that MENs are promising systems for effective CNS drug delivery and treatment for these diseases, however, further pre-clinical and clinical studies are required to achieve translation of this approach to the clinic.

Implantable Pulse Generators for Deep Brain Stimulation: Challenges, Complications, and Strategies for Practicality and Longevity.

Deep brain stimulation (DBS) represents an important treatment modality for movement disorders and other circuitopathies. Despite their miniaturization and increasing sophistication, DBS systems share a common set of components of which the implantable pulse generator (IPG) is the core power supply and programmable element. Here we provide an overview of key hardware and software specifications of commercially available IPG systems such as rechargeability, MRI compatibility, electrode configuration, pulse delivery, IPG case architecture, and local field potential sensing. We present evidence-based approaches to mitigate hardware complications, of which infection represents the most important factor. Strategies correlating positively with decreased complications include antibiotic impregnation and co-administration and other surgical considerations during IPG implantation such as the use of tack-up sutures and smaller profile devices.Strategies aimed at maximizing battery longevity include patient-related elements such as reliability of IPG recharging or consistency of nightly device shutoff, and device-specific such as parameter delivery, choice of lead configuration, implantation location, and careful selection of electrode materials to minimize impedance mismatch. Finally, experimental DBS systems such as ultrasound, magnetoelectric nanoparticles, and near-infrared that use extracorporeal powered neuromodulation strategies are described as potential future directions for minimally invasive treatment.