Magnetic torque-driven living microrobots for enhanced tumor infiltration

Bacterial microrobots combining self-propulsion and magnetic guidance are increasingly recognized as promising drug delivery vehicles for targeted cancer therapy. Thus far, control strategies have either relied on poorly scalable magnetic field gradients or employed directing magnetic fields with propulsive forces limited by the bacterial motor. Here, we present a magnetic torque-driven actuation scheme based on rotating magnetic fields to wirelessly control Magnetospirillum magneticum AMB-1 bearing versatile liposomal cargo. We observed a 4-fold increase in conjugate translocation across a model of the vascular endothelium and found that the primary mechanism driving this increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a 3D tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated the suitability of this magnetic stimulus for simultaneous actuation and inductive detection of AMB-1. Finally, we demonstrated that RMF significantly enhances AMB-1 tumor accumulation in vivo following systemic intravenous administration in mice. Our findings suggest that scalable magnetic torque-driven control strategies can be leveraged advantageously with biohybrid microrobots.

Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)-g-Chitosan Copolymer

Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties.

Magnetically Actuated Glaucoma Drainage Device with Adjustable Flow Properties after Implantation

Glaucoma is the second leading cause of preventable blindness worldwide, following cataract formation. A rise in the intraocular pressure (IOP) is a major risk factor for this disease, and results from an elevated resistance to aqueous humor outflow from the anterior chamber of the eye. Glaucoma drainage devices provide an alternative pathway through which the aqueous humor can effectively exit the eye, thereby lowering the IOP. However, post-operative IOP is unpredictable and current implants are deficient in maintaining IOP at optimal levels. To address this deficiency, we are developing an innovative, non-invasive magnetically actuated glaucoma implant with a hydrodynamic resistance that can be adjusted following surgery. This adjustment is achieved by integrating a magnetically actuated microvalve into the implant, which can open or close fluidic channels using an external magnetic stimulus. This microvalve was fabricated from poly(styrene–block–isobutylene–block–styrene), or ‘SIBS’, containing homogeneously dispersed magnetic microparticles. “Micro-pencil” valves of this material were fabricated using a combination of femtosecond laser machining with hot embossing. The glaucoma implant is comprised of a drainage tube and a housing element fabricated from two thermally bonded SIBS layers with the microvalve positioned in between. Microfluidic experiments involving actuating the magnetic micro-pencil with a moving external magnet confirmed the valving function. A pressure difference of around 6 mmHg was achieved, which is sufficient to overcome hypotony (i.e., too low IOP)—one of the most common post-operative complications following glaucoma surgery.

Paralleling insulated-gate bipolar transistors in the H-bridge structure to reduce current stress

In this study we present the new power electronic circuit implementation to create the arbitrary near-rectangular electromagnetic pulse. To this end, we develop a parallel- Insulated-gate bipolar transistors (IGBT)-based magnetic pulse generator utilizing the H-bridge architecture. This approach effectively reduces the current stress on the power switches while maintaining a simple structure using a single DC source and energy storage capacitor. Experimental results from the circuit characterization show that the proposed circuit is capable of repeatedly generating near-rectangular magnetic pulses and enables the generation of configurable and stable magnetic pulses without causing excessive device stresses. The introduced device enables the production of near-rectangular pulse trains for modulated magnetic stimuli. The maximum positive pulse width in the proposed neurostimulator is up to 600 µs, which is adjustable by the operator at the step resolution of 10 µs. The maximum transferred energy to the treatment coil was measured to be 100.4 J. The proposed transcranial magnetic stimulator (TMS) device enables more flexible magnetic stimulus shaping by H-bridge architecture and parallel IGBTs, which can effectively mitigate the current stress on power switches for repetitive treatment protocols.

Cortical silent period

The cortical silent period (cSP) refers to a period of suppression or silencing of ongoing electromyographic (EMG) activity during voluntary muscle contraction induced by a magnetic stimulus over the contralateral primary motor cortex. This chapter summarizes the physiological basis of the cSP, discusses technical aspects and recommendations on how to record and analyze it, and provides an overview of useful clinical applications. Evidence is presented that multiple spinal mechanisms are implicated in the initial part of the cSP, but some may be also active further on, whereas long-lasting cortical inhibitory mechanisms operate throughout the entire cSP, with an emphasis during its later part. The cSP is a highly relevant and clinically useful tool to assess inhibitory corticomotoneuronal mechanisms in health and disease.

Targeted Drug Delivery of Teniposide by Magnetic Nanocarrier

Background:: Drug delivery technologies adjust drug release profile, absorption, distribution, and elimination for benefiting to the improvement of product efficacy, effectiveness, and safety. The IONPs release drugs via enzymatic activity, changes in physiological conditions such as pH, osmolality radiation, or temperature. In the case of nanoparticles that respond to the magnetic stimulus, the drug directs its action towards the site of a detected magnetic field. Objective:: In this study, the synthesis of a specific drug-delivery system based on magnetic nanocarrier for teniposide as an anticancer drug is reported. The iron oxide@SiO2 core-shell nanoparticles were functionalized with APTS as a spacer then coupling to the DOTA molecules. Anticancer drug of teniposide conjugated to the acidic group of DOTA via an amide bond. Multi-purpose magnetic nanoparticles were synthesized for targeted delivery of teniposide. Methods: Iron oxide nanoparticles were firstly coated with silica and their surface was then modified with aminopropyltriethoxysilane (APTES) through an in situ method. DOTA-NHS was also coupled to Fe3O4@SiO2-APTES via an amide bond formation. In the final step, teniposide as an anti-cancer drug was conjugated with DOTA through ester bonds, and the final compound of Fe3O4@SiO2- APTES-DOTA-Teniposide was obtained. The obtained nanocarrier was evaluated by various analyses. Results:: The multifunctional Fe3O4@SiO2-APTES-DOTA nanocarriers were successfully synthesized and characterized by XRD, FTIR, TGA, and UV-vis techniques. The silica-coated magnetic nanoparticle functionalized with aminopropyl triethoxysilane (APTES) was reacted with an acid group of DOTA, and teniposide was then coupled to DOTA through ester formation bonds. Drug release experiments showed that most of the conjugated teniposide were released within the first 12h. Conclusion:: The fabricated nano-carriers exhibited pH-sensitive drug release behavior, which can minimize the non-specific systemic spread of toxic drugs during circulation whilst maximizing the efficiency of tumor-targeted anticancer drug delivery for this purpose. The prepared teniposidegrafted Fe3O4@SiO2-APTES-DOTA core–shell structure nanoparticles showed a magnetic property with exposure to magnetic fields, indicating a great potential application in the treatment of cancer using magnetic targeting drug-delivery technology and multimodal imaging techniques.

Stimulus Intensity Affects Variability of Motor Evoked Responses of the Non-Paretic, but Not Paretic Tibialis Anterior Muscle in Stroke

Background: Transcranial magnetic stimulus induced motor evoked potentials (MEPs) are quantified either with a single suprathreshold stimulus or using a stimulus response curve. Here, we explored variability in MEPs influenced by different stimulus intensities for the tibialis anterior muscle in stroke. Methods: MEPs for the paretic and non-paretic tibialis anterior (TA) muscle representations were collected from 26 participants with stroke at seven intensities. Variability of MEP parameters was examined with coefficients of variation (CV). Results: CV for the non-paretic TA MEP amplitude and area was significantly lower at 130% and 140% active motor threshold (AMT). CV for the paretic TA MEP amplitude and area did not vary with intensity. CV of MEP latency decreased with higher intensities for both muscles. CV of the silent period decreased with higher intensity for the non-paretic TA, but was in reverse for the paretic TA. Conclusion: We recommend a stimulus intensity of greater than 130% AMT to reduce variability for the non-paretic TA. The stimulus intensity did not affect the MEP variability of the paretic TA. Variability of MEPs is affected by intensity and side tested (paretic and non-paretic), suggesting careful selection of experimental parameters for testing.

Field-Dependent Stiffness of a Soft Structure Fabricated from Magnetic-Responsive Materials: Magnetorheological Elastomer and Fluid

A very flexible structure with a tunable stiffness controlled by an external magnetic stimulus is presented. The proposed structure is fabricated using two magnetic-responsive materials, namely a magnetorheological elastomer (MRE) as a skin layer and a magnetorheological fluid (MRF) as a core to fill the void channels of the skin layer. After briefly describing the field-dependent material characteristics of the MRE and MRF, the fabrication procedures of the structure are provided in detail. The MRE skin layer is produced using a precise mold with rectangular void channels to hold the MRF. Two samples are produced, namely with and without MRF, to evaluate the stiffness change attributed to the MRF. A magnetic field is generated using two permanent magnets attached to a specialized jig in a universal tensile machine. The force-displacement relationship of the two samples are measured as a function of magnetic flux density. Stiffness change is analyzed at two different regions, namely a small and large deformation region. The sample with MRF exhibits much higher stiffness increases in the small deformation region than the sample without MRF. Furthermore, the stiffness of the sample with MRF also increases in the large deformation region, while the stiffness of the sample without MRF remains constant. The inherent and advantageous characteristics of the proposed structure are demonstrated through two conceptual applications, namely a haptic rollable keyboard and a smart braille watch.