Soft erythrocyte-based bacterial microswimmers for cargo delivery

Abstract

Bacteria-propelled biohybrid microswimmers have recently shown to be able to actively transport and deliver cargos encapsulated into their synthetic constructs to specific regions locally. However, usage of synthetic materials as cargo carriers can result in inferior performance in load-carrying efficiency, biocompatibility, and biodegradability, impeding clinical translation of biohybrid microswimmers. Here, we report construction and external guidance of bacteria-driven microswimmers using red blood cells (RBCs; erythrocytes) as autologous cargo carriers for active and guided drug delivery. Multifunctional biohybrid microswimmers were fabricated by attachment of RBCs [loaded with anticancer doxorubicin drug molecules and superparamagnetic iron oxide nanoparticles (SPIONs)] to bioengineered motile bacteria, Escherichia coli MG1655, via biotin-avidin-biotin binding complex. Autonomous and on-board propulsion of biohybrid microswimmers was provided by bacteria, and their external magnetic guidance was enabled by SPIONs loaded into the RBCs. Furthermore, bacteria-driven RBC microswimmers displayed preserved deformability and attachment stability even after squeezing in microchannels smaller than their sizes, as in the case of bare RBCs. In addition, an on-demand light-activated hyperthermia termination switch was engineered for RBC microswimmers to control bacteria population after operations. RBCs, as biological and autologous cargo carriers in the biohybrid microswimmers, offer notable advantages in stability, deformability, biocompatibility, and biodegradability over synthetic cargo-carrier materials. The biohybrid microswimmer design presented here transforms RBCs from passive cargo carriers into active and guidable cargo carriers toward targeted drug and other cargo delivery applications in medicine.

Irreversible hydrodynamic trapping by surface rollers

“…A wide range of physical mechanics may be exploited to achieve these tasks, giving rise to optical [12], magnetic [5], electrostatic [21], or hydrodynamic forces [28]. In recent years, synthetic swimmers actuated by external fields, chemical fuels or bacteria have been attracting attention and been employed successfully for the transport of cargo towards biomedical applications [1,9,18,32].…”

A stochastic model for bacteria-driven micro-swimmers

“…The assumption of a chemically permeable particle could also be relaxed, and the perturbation to the concentration field by the presence of the particle (and the cells) should be solved for. Another possible extension is the study of deformable random walkers, inspired by experiments with bacteria-driven micro-swimmers in which E. coli are attached to red blood cells 47 . One of the ultimate applications of bacteria-driven micro-swimmers is targeted drug delivery, which requires a suspension of these particles to move collectively.…”

Engineering E. coli for magnetic control and the spatial localization of functions

“…Despite several attempts to use magnetotactic bacteria 29 , they remained difficult to harness 30 and to manipulate genetically. One second strategy consisted in building bacterial biohybrid systems either using magnetotactic bacteria carrying cargo-particles 31,32 , or reciprocally, using a magnetic field to control the orientation of motile bacteria linked to magnetic beads 33,34 . A third approach aimed to magnetize naturally diamagnetic microorganisms or eukaryotic cells by over-expressing iron-storage ferritins or iron-binding proteins inside their cytoplasm.…”