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.

Magnetically driven in-plane modulation of the 3D orientation of vertical ferromagnetic flakes.

External magnetic fields are known to attract and orient magnetically responsive colloidal particles. In the case of 2D microplatelets, rotating magnetic fields are typically used to orient them parallel to...

Rotating Magnetic Fields Inhibit Mitochondrial Respiration, Promote Oxidative Stress and Produce Loss of Mitochondrial Integrity in Cancer Cells

Electromagnetic fields (EMF) raise intracellular levels of reactive oxygen species (ROS) that can be toxic to cancer cells. Because weak magnetic fields influence spin state pairing in redox-active radical electron pairs, we hypothesize that they disrupt electron flow in the mitochondrial electron transport chain (ETC). We tested this hypothesis by studying the effects of oscillating magnetic fields (sOMF) produced by a new noninvasive device involving permanent magnets spinning with specific frequency and timing patterns. We studied the effects of sOMF on ETC by measuring the consumption of oxygen (O2) by isolated rat liver mitochondria, normal human astrocytes, and several patient derived brain tumor cells, and O2 generation/consumption by plant cells with an O2 electrode. We also investigated glucose metabolism in tumor cells using 1H and 13C nuclear magnetic resonance and assessed mitochondrial alterations leading to cell death by using fluorescence microscopy with MitoTracker™ and a fluorescent probe for Caspase 3 activation. We show that sOMF of appropriate field strength, frequency, and on/off profiles completely arrest electron transport in isolated, respiring, rat liver mitochondria and patient derived glioblastoma (GBM), meningioma and diffuse intrinsic pontine glioma (DIPG) cells and can induce loss of mitochondrial integrity. These changes correlate with a decrease in mitochondrial carbon flux in cancer cells and with cancer cell death even in the non-dividing phase of the cell cycle. Our findings suggest that rotating magnetic fields could be therapeutically efficacious in brain cancers such as GBM and DIPG through selective disruption of the electron flow in immobile ETC complexes.

The FFLO State in the Dimer Mott Organic Superconductor κ-(BEDT-TTF)2Cu[N(CN)2]Br

The superconducting phase diagram for a quasi-two-dimensional organic superconductor, κ-(BEDT-TTF)2Cu[N(CN)2]Br, was studied using pulsed magnetic field penetration depth measurements under rotating magnetic fields. At low temperatures, Hc2 was abruptly suppressed even by small tilts of the applied fields owing to the orbital pair-breaking effect. In magnetic fields parallel to the conducting plane, the temperature dependence of the upper critical field Hc2 exhibited an upturn and exceeded the Pauli limit field HP in the lower temperature region. Further analyses with the second derivative of the penetration depth showed an anomaly at 31–32 T, which roughly corresponded to HP. The origin of the anomaly should not be related to the orbital effect, but the paramagnetic effect, which is almost isotropic in organic salts, because it barely depends on the field angle. Based on these results, the observed anomaly is most likely due to the transition between the Bardeen-Cooper-Schrieffer (BCS) and the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) states. Additionally, we discuss the phase diagram and physical parameters of the transition by comparing them with other FFLO candidates.

The effect of a magnetic field on the phenolic composition and virus sanitation of raspberry plants

A magnetic pulse treatment led to an increase in the Raspberry bushy dwarf Idaeovirus-free microplants’ output and their phenolic composition change. The greatest output of the virus-free raspberries microplants (80–82%) was marked after complex treatment with pulsed and rotating magnetic fields with a time-changing frequency from 3.2 to 51 Hz, as well as with a pulsed magnetic field with a frequency from 1 to 10 Hz. The pulsed and rotating magnetic fields’ complex effect resulted in the gallic and salicylic acid content increase by 14 % and 71%, respectively, compared to the untreated variant. The chlorogenic, salicylic and gallic acids’ active synthesis was observed 72 hours after the magnetic treatment with a frequency from 3.2 to 51 Hz. There was a tendency for the amount of the phenolcarbonic acid to decrease 14 days after the magnetic treatment, except for the variant with the pulsed and rotating field treatment.

Soft Capsule Magnetic Millirobots for Region-Specific Drug Delivery in the Central Nervous System

Small soft robotic systems are being explored for myriad applications in medicine. Specifically, magnetically actuated microrobots capable of remote manipulation hold significant potential for the targeted delivery of therapeutics and biologicals. Much of previous efforts on microrobotics have been dedicated to locomotion in aqueous environments and hard surfaces. However, our human bodies are made of dense biological tissues, requiring researchers to develop new microrobotics that can locomote atop tissue surfaces. Tumbling microrobots are a sub-category of these devices capable of walking on surfaces guided by rotating magnetic fields. Using microrobots to deliver payloads to specific regions of sensitive tissues is a primary goal of medical microrobots. Central nervous system (CNS) tissues are a prime candidate given their delicate structure and highly region-specific function. Here we demonstrate surface walking of soft alginate capsules capable of moving on top of a rat cortex and mouse spinal cord ex vivo, demonstrating multi-location small molecule delivery to up to six different locations on each type of tissue with high spatial specificity. The softness of alginate gel prevents injuries that may arise from friction with CNS tissues during millirobot locomotion. Development of this technology may be useful in clinical and preclinical applications such as drug delivery, neural stimulation, and diagnostic imaging.