Engineering Magnetotactic Bacteria as Medical Microrobots

Abstract

Nature's ability to create complex and functionalized organisms has long inspired engineers and scientists to develop increasingly advanced machines. Magnetotactic bacteria (MTB), a group of Gram-negative prokaryotes that biomineralize iron and thrive in aquatic environments, have garnered significant attention from the bioengineering community. These bacteria possess chains of magnetic nanocrystals known as magnetosomes, which allow them to align with Earth's geomagnetic field and navigate through aquatic environments via magnetotaxis, enabling localization to areas rich in nutrients and optimal oxygen concentration. Their built-in magnetic components, along with their intrinsic and/or modified biological functions, make them one of the most promising platforms for future medical microrobots. Leveraging an externally applied magnetic field, the motion of MTBs can be precisely controlled, rendering them suitable for use as a new type of biohybrid microrobotics with great promise in medicine for bioimaging, drug delivery, cancer therapy, antimicrobial treatment, and detoxification. This mini-review provides an up-to-date overview of recent advancements in MTB microrobots, delineates the interaction between MTB microrobots and magnetic fields, elucidates propulsion mechanisms and motion control, and reports state-of-the-art strategies for modifying and functionalizing MTB for medical applications.

Keywords: bioimaging; cancer therapy; drug delivery; magnetotactic bacteria; microrobotics.

Figure 1

Schematic illustration of locomotion, targeting, functionalization, and biomedical applications of MTB microrobots. Adapted with permission.^{[ 43 ]} Copyright 2014, American Chemical Society. Adapted with permission.^{[ 44 ]} Copyright 2021, Wiley‐VCH GmbH. Adapted with permission.^{[ 45 ]} Copyright 2016, American Society for Microbiology. Adapted under the terms of the CC BY 4.0 license.^{[ 46 ]} Copyright 2021, MDPI. Adapted with permission.^{[ 47 ]} Copyright 2022, American Chemical Society. Adapted with permission.^{[ 48 ]} Copyright 2022, Elsevier.

Figure 2

a) Typical structure of a magnetotactic bacterium. Adapted with permission.^{[ 49 ]} Copyright 2020, Springer Nature. b) Hypothesized mechanism of magnetite biomineralization to form magnetosomes. Adapted with permission.^{[ 50 ]} Copyright 2021, Springer Nature.

Figure 3

Schematic illustration of the various actuation strategies of MTB microrobots. Adapted with permission.^{[ 40 ]} Copyright 2022, American Association for the Advancement of Science.

Figure 4

Functionalization of MTB. a) Binding of nanoliposomes to the surface of MTB (MC‐1) by amide bond conjugation. Reproduced with permission.^{[ 43 ]} Copyright 2014, American Chemical Society. b) Coating MTB (AMB‐1) with the nanophotosensitizer INPs by maleimide‐thiol conjugation via a Michael addition reaction. Reproduced with permission.^{[ 44 ]} Copyright 2021, Wiley‐VCH GmbH. c) Attachment of antibody‐coated MTB (MO‐1) to S. aureus via affinity binding between S. aureus surface protein and MTB surface antibodies. Reproduced with permission.^{[ 45 ]} Copyright 2016, American Society for Microbiology. d) Magnetosome aggregation because of the separation of vesicles and filaments in mutant MTB. Reproduced with permission.^{[ 73 ]} Copyright 2006, Springer Nature.

Figure 5

Bioimaging applications of MTB microrobots. a) Magnetic resonance imaging. b) Magnetic particle imaging. c) Fluorescence imaging. d) Bioluminescence imaging. e) Photothermal imaging. f) Magnetic hyperthermia imaging. Reproduced with permission.^{[ 79 ]} Copyright 2022, American Chemical Society. Reproduced with permission.^{[ 44 ]} Copyright 2021, Wiley‐VCH GmbH. Reproduced with permission.^{[ 47 ]} Copyright 2022, American Chemical Society.

Figure 6

Anti‐tumor applications of MTB microrobots. a) Magnetic fields used to potentially deliver active substances to solid tumors through Nanoliposome‐attached MTB microrobots. Reproduced with permission.^{[ 43 ]} Copyright 2014, American Chemical Society. b) Delivery of drug‐containing nanoliposomes to tumor hypoxic regions by MTB microrobots. Reproduced with permission.^{[ 80 ]} Copyright 2016, Springer Nature. c) Tumor inhibition by activation of calcium influx via magneto‐mechanical stimulus exerted by MTB. Reproduced with permission.^{[ 48 ]} Copyright 2022, Elsevier. d) Magnetic hyperthermia tumor therapy of MTB microrobots under an alternating magnetic field. Reproduced with permission.^{[ 47 ]} Copyright 2022, American Chemical Society. e) Sequential magneto‐actuated and optics‐triggered MTB microrobots for targeted cancer therapy. Reproduced with permission.^{[ 44 ]} Copyright 2021, Wiley‐VCH GmbH. f) Magnetic torque–driven MTB living microrobots to increase tumor infiltration. Reproduced with permission.^{[ 40 ]} Copyright 2022, American Association for the Advancement of Science.

Figure 7

Antimicrobial applications of MTB microrobots. a) Schematic diagram of MTB (MO‐1) functionalized with rabbit anti‐MO‐1 polyclonal antibody binding to S. aureus, inducing bacterial damage upon exposure to SMF. Reproduced with permission.^{[ 85 ]} Copyright 2017, Elsevier. b) SEM of MSR‐1 cells captured within a microtube. The inset shows a higher magnification view of the bacteria within the tube, with a scale bar of 500 nm. (Left). Bright‐field microscopy images of MSR‐1‐powered biohybrid swimming (Right). c) Magnetic guidance of biohybrids to E. coli biofilms. d) Increased magnification displays EPS and bacteria surrounding the biohybrid. Reproduced with permission.^{[ 86 ]} Copyright 2017, American Chemical Society. e) The migration of MO‐1 within a microfluidic chip under the influence of applied magnetic fields. f) The killing effect of antibody‐conjugated MO‐1 cells on S. aureus under the SMF. Reproduced with permission.^{[ 78 ]} Copyright 2017, Elsevier.

Figure 8

Applications of MTB microrobots for toxin removal. a) Schematic diagram of MTB (AMB‐1) motion behaviors for pesticide removal. Maneuvering is achieved using a custom‐made controllable magnetic field. Reproduced under the terms of the CC BY 4.0 license.^{[ 87 ]} Copyright 2023, American Chemical Society. b) Scheme of magnetic separation of metal‐loaded MTB (KTN90) for the bioremediation processes. Reproduced with permission.^{[ 88 ]} Copyright 2016, Springer Nature.