An Engineered Bacteria-Hybrid Microrobot with the Magnetothermal Bioswitch for Remotely Collective Perception and Imaging-Guided Cancer Treatment

Abstract

Microrobots driven by multiple propelling forces hold great potential for noninvasively targeted delivery in the physiologic environment. However, the remotely collective perception and precise propelling in a low Reynold’s number bioenvironment remain the major challenges of microrobots to achieve desired therapeutic effects in vivo. Here, we reported a biohybrid microrobot that integrated with magnetic, thermal, and hypoxia sensitivities and an internal fluorescent protein as the dual reporter of thermal and positioning signals for targeted cancer treatment. There were three key elements in the microrobotic system, including the magnetic nanoparticle (MNP)-loaded probiotic Escherichia coli Nissle1917 (EcN@MNP) for spatially magnetic and hypoxia perception, a thermal-logic circuit engineered into the bacteria to control the biosynthesis of mCherry as the temperature and positioning reporter, and NDH-2 enzyme encoded in the EcN for enhanced anticancer therapy. According to the fluorescent-protein-based imaging feedback, the microrobot showed good thermal sensitivity and active targeting ability to the tumor area in a collective manner under the magnetic field. The cancer cell apoptosis was efficiently triggered in vitro and in vivo by the hybrid microrobot coupled with the effects of magnetothermal ablation and NDH-2-induced reactive oxygen species (ROS) damage. Our study demonstrates that the biohybrid EcN microrobot is an ideal platform to integrate the physical, biological, and chemical properties for collective perception and propelling in targeted cancer treatment.

Magnetic torque–driven living microrobots for increased tumor infiltration

“…Magnetically responsive bacteria include strains rendered magnetic through conjugation with magnetic materials (18)(19)(20) and magnetotactic bacteria (MTB), which are innately magnetic. In their native aquatic habitats, MTB typically biomineralize stably magnetized anisotropic chains of magnetite nanocrystals and use magnetically assisted aerotaxis to migrate to regions of low oxygen concentration.…”

“Double-Effect” strategy against Triple-Negative Breast Cancer via a synergistic therapy of Magneto-mechanical Force enhancing NIR-II Hypothermal Ablation

“…Conversely, exposure of pure cells (without internalized MPCs) to RMF did not inhibit their viability (Figures 2b, c ). Interestingly, under the effect of RMF at 60 mT for 2 h, the cell viability showed a trend of decreasing at first and afterwards increasing with the increased magnetic field frequency in Figure 2d , indicating that MPCs and RMF reached the maximum synchronization frequency of 15 Hz [26]. Hence, the mechanical killing of MPCs under this setting displayed the strongest mechanical performance with an optimal cell lethality ratio of 23%.…”

Stimuli-Activable Metal-Bearing Nanomaterials and Precise On-Demand Antibacterial Strategies

“…Magnetothermal therapy has been often combined with chemotherapy, photodynamic therapy, and photothermal therapy to achieve synergistic effects but mostly for cancer treatment rather than antibacterial activity. − One of the few studies that combines magnetothermal therapy for synergistic antibacterial activity was the magnetothermal–chemo synergistic strategy developed by Luengo’s group . In this study, a γ-Fe 2 O 3 /Ag nanocomposite was synthesized via silver nitrate reduction in the presence of superparamagnetic γ-Fe 2 O 3 NPs.…”