Ali Hadjikhani

Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles.

It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.

Magnetoelectric ‘spin’ on stimulating the brain

AIM The in vivo study on imprinting control region mice aims to show that magnetoelectric nanoparticles may directly couple the intrinsic neural activity-induced electric fields with external magnetic fields. METHODS Approximately 10 µg of CoFe2O4-BaTiO3 30-nm nanoparticles have been intravenously administrated through a tail vein and forced to cross the blood-brain barrier via a d.c. field gradient of 3000 Oe/cm. A surgically attached two-channel electroencephalography headmount has directly measured the modulation of intrinsic electric waveforms by an external a.c. 100-Oe magnetic field in a frequency range of 0-20 Hz. RESULTS The modulated signal has reached the strength comparable to that due the regular neural activity. CONCLUSION The study opens a pathway to use multifunctional nanoparticles to control intrinsic fields deep in the brain.

Two-Dimensional Vanadium Carbide (MXene) as a High-Capacity Cathode Material for Rechargeable Aluminum Batteries

Rechargeable aluminum batteries (Al batteries) can potentially be safer, cheaper, and deliver higher energy densities than those of commercial Li-ion batteries (LIBs). However, due to the very high charge density of Al3+ cations and their strong interactions with the host lattice, very few cathode materials are known to be able to reversibly intercalate these ions. Herein, a rechargeable Al battery based on a two-dimensional (2D) vanadium carbide (V2CTx) MXene cathode is reported. The reversible intercalation of Al3+ cations between the MXene layers is suggested to be the mechanism for charge storage. It was found that the electrochemical performance could be significantly improved by converting multilayered V2CTx particles to few-layer sheets. With specific capacities of more than 300 mAh g-1 at high discharge rates and relatively high discharge potentials, V2CTx MXene electrodes show one of the best performances among the reported cathode materials for Al batteries. This study can lead to foundations for the development of high-capacity and high energy density rechargeable Al batteries by showcasing the potential of a large family of intercalation-type cathode materials based on MXenes.

Biodistribution and clearance of magnetoelectric nanoparticles for nanomedical applications using energy dispersive spectroscopy

AIM The biodistribution and clearance of magnetoelectric nanoparticles (MENs) in a mouse model was studied through electron energy dispersive spectroscopy. MATERIALS & METHODS This approach allows for detection of nanoparticles (NPs) in tissues with the spatial resolution of scanning electron microscopy, does not require any tissue-sensitive staining and is not limited to MENs. RESULTS The size-dependent biodistribution of intravenously administrated MENs was measured in vital organs such as the kidneys, liver, spleen, lungs and brain at four different postinjection times including 1 day, 1 week, 4 and 8 weeks, respectively. CONCLUSION The smallest NPs, 10-nm MENs, were cleared relatively rapidly and uniformly across the organs, while the clearance of the larger NPs, 100- and 600-nm MENs, was highly nonlinear with time and nonuniform across the organs.

The Physics of Spin-Transfer Torque Switching in Magnetic Tunneling Junctions in Sub-10 nm Size Range

The spin-transfer torque magnetic tunneling junction (MTJ) technology may pave a way to a universal memory paradigm. MTJ devices with perpendicular magnetic anisotropy have the potential to have high thermal stability, high tunneling magnetoresistance, and low critical current for energy-efficient current-induced magnetization switching. Using devices fabricated through focused ion beam etching with Ga- and Ne-ion beams, this paper aimed to understand the size dependence of the current/voltage characteristics in the sub-10 nm range. The switching current density drastically dropped around 1 MA/cm2 as the device size was reduced below 10 nm. A stability of over 22 kT measured for a 5 nm device indicated a significantly reduced spin relaxation time.

Abstract B47: A novel mechanism for field-controlled high-specificity targeted anticancer drug delivery and on-demand release using magnetoelectric nanoparticles

Background: An important challenge in chemotherapy is targeted drug delivery to eradicate tumor cells while sparing normal cells. The circulatory system can deliver a drug to almost every cell in the body; however, delivering the drug specifically into the tumor cell and then releasing it on demand remains a formidable task. Nanoparticles posses unique properties to address this issue. Despite their great potential, a significant problem remains to ensure that the drug is not prematurely released in the plasma or interstitial space but is released at an appropriate rate once at the target site. Recently, we discovered a new class of “smart” multifunctional nanostructures known as magnetoelectric nanoparticles (MENs) that enables a high-efficacy “communication” between intrinsic electric fields at the intra-cellular level, which are inherent to the cellular membrane nature, and external magnetic fields, to control targeted drug delivery and release into specific tumor cells on demand. Herein, the results of a comprehensive in vitro study and an in vivo study on using MENs to treat ovarian cancer (OC) are presented. Methods: A specific combination of d.c. and a.c.-magnetic fields is used to externally control and separate delivery and release functions, respectively. MENs in a wide diameter range, 5-1000nm, are made of coreshell CoFe2O4@BaTiO3 nanostructures. The novel approach is compared to current state-of-the-art nanotechnology deliveries including (i) active immunochemotherapeutic approaches using polymer nanoparticles conjugated with monoclonal antibodies (mAbs) and (ii) passive enhanced permeability and retention (EPR)-based approach using polymer nanoparticles without any immunoactive reagents. Mitotic inhibitor paclitaxel (PTX)–loaded MENs are administrated through systemic IV injection into a lateral tail vein or through localized subcutaneous injection directly into the tumor site. The tumor progression is monitored through infrared (IR) imaging witth mAb-conjugated fluorescent agent Her2Sense 645. Post euthanasia, the cell morphology and the tumor presence in different organs are further studied with HE 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B47.

Magnetoelectric nanoparticles for delivery of antitumor peptides into glioblastoma cells by magnetic fields

AIM We studied externally controlled anticancer effects of binding tumor growth inhibiting synthetic peptides to magnetoelectric nanoparticles (MENs) on treatment of glioblastomas. METHODS Hydrothermally synthesized 30-nm MENs had the core-shell composition of CoFe2O4@BaTiO3. Molecules of growth hormone-releasing hormone antagonist of the MIA class (MIA690) were chemically bound to MENs. In vitro experiments utilized human glioblastoma cells (U-87MG) and human brain microvascular endothelial cells. RESULTS The studies demonstrated externally controlled high-efficacy binding of MIA690 to MENs, targeted specificity to glioblastoma cells and on-demand release of the peptide by application of d.c. and a.c. magnetic fields, respectively. CONCLUSION The results support the use of MENs as an effective drug delivery carrier for growth hormone-releasing hormone antagonists in the treatment of human glioblastomas.

Properties of magnetic tunneling junction devices with characteristic sizes in sub-5-nm range

Nanomagnetic devices in the sub-5-nm size range still do not exist, not only because of many fabrication and characterization challenges but also because of the poorly understood physics in this size range. Previous experimental studies from various groups have shown that the spin relaxation time can be increased by orders of magnitude with this size reduction. The increased spin lifetime leads to a combination of effects such as spin accumulation and tunneling magnetoresistance enhancement which in turn can significantly and favorably affect the device performance [1]. The goal of this study is to exploit this new physics through fabrication and testing of magnetic tunneling junction (MTJ) devices with a characteristic size of below 5 nm. To achieve this goal, we integrate magnetic nanoparticles into MTJ structures and measure their key properties such as I-V curves and magnetoresistance dependencies. The nanoparticles, with sizes ranging from below 2 to over 10 nm, are made of the ferrimagnetic spinel ferrite CoFe2O4 using co-precipitation chemistry. It has been theoretically predicted that these nanoparticles become half-metallic in this size range and thus can lead to unprecedented high magnetoresistance values. Indeed, the nanodevices under study display spin-filtering properties, as confirmed through measurements of magnetoresistance and I-V dependences [2]. This paper summarizes the measured room-temperature anomalous magnetoresistance and I-V curves with a Coulomb-staircase-like dependence characteristic of a single-electron transport.

Anomalous properties of sub-10-nm magnetic tunneling junctions

Magnetic logic devices have advantages of non-volatility, radiation hardness, scalability down to the sub-5-nm range, and three-dimensional (3D) integration capability. Despite these advantages, nanomagnetic applications for information processing are limited today. The main stumbling block is the inadequately high energy required to switch information states in the spin-based nanodevices. Recently, the spin-transfer torque (STT) effect has been introduced as a promising solution [1-2]. In STT magnetic tunneling junctions (MTJs), using a spin-polarized electric current to switch magnetic states has the potential to solve the energy problem. However, the switching current density on the order of 1 MA/cm2 in the current STT-MTJ devices, with the smallest reported to date characteristic cross-sectional size on the order of 10 nm, still remains inadequately high for enabling a wide range of information processing applications [3-4]. For the technology to be competitive in the near future, it is critical to show that it could be favorably scaled into the sub-10-nm range. On a positive note, due to a new physics in this previously poorly explored size range, nanomagnetic devices may display promising characteristics that can make them superior to their semiconductor counterparts. In this size range, the underlying spin physics is due to the surface as much as it is due the volume. As a result, the effective thermal reservoir that absorbs spin excitations is substantially reduced, which in turn leads to a reduced spin damping and consequently to a reduced switching current density. Hence, the current study to understand the junction size dependence of the spin switching current is timely. This paper presents the key results of this study.

Effect of platinum metallization in cofired platinum / alumina microsystems for implantable medical applications

Typically, hermetic feedthroughs for implantable devices, such as pacemakers, use an alumina ceramic insulator brazed to a platinum wire pin. This material combination has a long history in implantable devices and is the desired structure due to the acceptance by the FDA for implantable hermetic feedthroughs. The growing demand for increased input/output (I/O) hermetic feedthroughs for implantable neural stimulator applications can be addresses by developing a new, co-fired platinum/alumina multilayer ceramic technology in a configuration that supports 300 plus I/Os, which is not commercially available. Different densification rate of platinum and alumina is the major issue in developing a high-density feedthrough. This difference in densification rate could create delamination and crack in feedthrough structure and decrease the reliability and degree of the hermeticty of the final assembly. In this paper different metallization were evaluated to minimize this difference. Additionaly the firing atmosphere...