Magnetic torque-driven living microrobots for enhanced tumor infiltration

Abstract

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.

Bacterial‐Mediated Tumor Therapy: Old Treatment in a New Context

“…[161] Gwisai et al integrated magnetic nanoparticles and nanoliposomes loaded with photothermal agents (indocyanine green (ICG)) and chemotherapeutic molecules (DOX) onto E. coli with an efficiency of ≈90% to form a magnetic controlled bacterial biological hybrid. [162] Chemotherapeutic agent 5-fluorouracil (FU) and macrophage phenotype regulator zoledronic acid (ZOL) were loaded into EcN through electroporation, followed by decoration of Au nanorods on the ECN surface to construct EcN Z/F @Au. An intermittent near-infrared (NIR) illumination Reproduced with permission.…”

Printing on Particles: Combining Two‐Photon Nanolithography and Capillary Assembly to Fabricate Multimaterial Microstructures

“…The actuation of the magnetic structures was achieved using a small-scale arbitrary magnetic field generator consisting of eight electromagnets arranged in a single hemisphere, which was used to apply RMF (MFG-100-i, MagnebotiX, Zürich, Switzerland). [50] The system was integrated with an inverted microscope (Nikon Eclipse Ti2). Samples were positioned between the objective lens and the hemisphere of the electromagnets.…”

A Review of Soft Microrobots: Material, Fabrication, and Actuation

“…With the unique functional characteristics of high affinity, excellent adaptability, and natural self-actuation capability, live organisms (such as sperm cells, [86] red blood cells (RBCs), [87,164] bacteria, [25] cardiomyocytes, [89] and neutrophil cells (NEs) [165] ) have also been used in a series of attractive research about soft microrobots. [24,43,61] Live organisms have internal sensory units that can dynamically interact with external environments, such as oxygen, chemicals, pH, and temperature gradient.…”

“…that can react to external stimulations. [25] As organisms have natural biocompatibility and inner perception in the internal environment of the body, biological soft microrobots have advantages for applications of in vivo cargo transportation [26] and cell therapy. [27] Like the integration of the previous two kinds of soft microrobots, biohybrid soft microrobots comprise artificial anchors and living biological organisms.…”