Multifunctional Bacteria-Driven Microswimmers for Targeted Active Drug Delivery

High-performance, multifunctional bacteria-driven microswimmers are introduced using an optimized design and fabrication method for targeted drug delivery applications. These microswimmers are made of mostly single <i>Escherichia coli</i> bacterium attached to the surface of drug-loaded polyelectrolyte multilayer (PEM) microparticles with embedded magnetic nanoparticles. The PEM drug carriers are 1 μm in diameter and are intentionally fabricated with a more viscoelastic material than the particles previously studied in the literature. The resulting stochastic microswimmers are able to swim at mean speeds of up to 22.5 μm/s. They can be guided and targeted to specific cells, because they exhibit biased and directional motion under a chemoattractant gradient and a magnetic field, respectively. Moreover, we demonstrate the microswimmers delivering doxorubicin anticancer drug molecules, encapsulated in the polyelectrolyte multilayers, to 4T1 breast cancer cells under magnetic guidance <i>in vitro</i>. The results reveal the feasibility of using these active multifunctional bacteria-driven microswimmers to perform targeted drug delivery with significantly enhanced drug transfer, when compared with the passive PEM microparticles

Microemulsion-Based Soft Bacteria-Driven Microswimmers for Active Cargo Delivery

Biohybrid cell-driven microsystems offer unparalleled possibilities for realization of soft microrobots at the micron scale. Here, we introduce a bacteria-driven microswimmer that combines the active locomotion and sensing capabilities of bacteria with the desirable encapsulation and viscoelastic properties of a soft double-micelle microemulsion for active transport and delivery of cargo (<i>e</i>.<i>g</i>., imaging agents, genes, and drugs) to living cells. Quasi-monodisperse double emulsions were synthesized with an aqueous core that encapsulated the fluorescence imaging agents, as a proof-of-concept cargo in this study, and an outer oil shell that was functionalized with streptavidin for specific and stable attachment of biotin-conjugated <i>Escherichia coli</i>. Motile bacteria effectively propelled the soft microswimmers across a Transwell membrane, actively delivering imaging agents (<i>i</i>.<i>e</i>., dyes) encapsulated inside of the micelles to a monolayer of cultured MCF7 breast cancer and J744A.1 macrophage cells, which enabled real-time, live-cell imaging of cell organelles, namely mitochondria, endoplasmic reticulum, and Golgi body. This <i>in vitro</i> model demonstrates the proof-of-concept feasibility of the proposed soft microswimmers and offers promise for potential biomedical applications in active and/or targeted transport and delivery of imaging agents, drugs, stem cells, siRNA, and therapeutic genes to live tissue in <i>in vitro</i> disease models (<i>e</i>.<i>g</i>., organ-on-a-chip devices) and stagnant or low-flow-velocity fluidic regions of the human body

Microemulsion-Based Soft Bacteria-Driven Microswimmers for Active Cargo Delivery

Biohybrid cell-driven microsystems offer unparalleled possibilities for realization of soft microrobots at the micron scale. Here, we introduce a bacteria-driven microswimmer that combines the active locomotion and sensing capabilities of bacteria with the desirable encapsulation and viscoelastic properties of a soft double-micelle microemulsion for active transport and delivery of cargo (<i>e</i>.<i>g</i>., imaging agents, genes, and drugs) to living cells. Quasi-monodisperse double emulsions were synthesized with an aqueous core that encapsulated the fluorescence imaging agents, as a proof-of-concept cargo in this study, and an outer oil shell that was functionalized with streptavidin for specific and stable attachment of biotin-conjugated <i>Escherichia coli</i>. Motile bacteria effectively propelled the soft microswimmers across a Transwell membrane, actively delivering imaging agents (<i>i</i>.<i>e</i>., dyes) encapsulated inside of the micelles to a monolayer of cultured MCF7 breast cancer and J744A.1 macrophage cells, which enabled real-time, live-cell imaging of cell organelles, namely mitochondria, endoplasmic reticulum, and Golgi body. This <i>in vitro</i> model demonstrates the proof-of-concept feasibility of the proposed soft microswimmers and offers promise for potential biomedical applications in active and/or targeted transport and delivery of imaging agents, drugs, stem cells, siRNA, and therapeutic genes to live tissue in <i>in vitro</i> disease models (<i>e</i>.<i>g</i>., organ-on-a-chip devices) and stagnant or low-flow-velocity fluidic regions of the human body