Abstract

In the past decade, versatile micro- and nanosized machines have emerged as active agents for large-scale detoxification, sensing, microfabrication, and many other promising applications. Micromachines have also been envisioned as the next advancement in dynamic therapy with numerous proof-of-concept studies in drug delivery, microsurgery, and detoxification. However, the practical use of synthetic micromotors in the body requires the development of fully biocompatible designs facilitating micromotor movement in biological fluids of diverse composition and displaying desired functions in specific locations. The combination of the efficient movement of synthetic micromotors with the biological functions of natural cells has resulted in cell-like micromotors with expanded therapeutic and toxin-removing capabilities toward different biological applications. Thus, these biocompatible and biomimetic cell-like micromotors can provide efficient movement in complex biofluids and mimic the functionalities of natural cells. This Account highlights a variety of recent proof-of-concept examples of cell-like micromotors, based on different designs and actuation mechanisms, which perform diverse in vivo tasks. The cell-like micromotors are divided into two groups: (i) cell membrane-coated micromotors, which use natural cell membranes derived from red blood cells, platelets, or a combination of different cells to cloak and functionalize synthetic motors, and (ii) cell-based micromotors, which directly use entire cells such as blood cells, spermatozoa, and bacteria as the micromotor engine. Cell-like micromotors, composed of different cellular components and actuated by different mechanisms, have shown unique advantages for operation in complex biofluids such as blood. Due to the inherent biocompatibility of cell-derived materials, these cell-like micromotors do not provoke an immune response while utilizing useful secondary functions of the blood cells such as strong ability to soak up foreign agents or bind toxins. Additionally, the utilization of autonomously motile cells (e.g., bacteria) allows for built-in chemotactic motion, which eliminates the need for harmful fuels or complex actuation equipment. Furthermore, a broad range of cells, both passive and motile, can be incorporated into micromachine designs constituting a large library of functional components depending on the limits of the desired application. The coupling of cellular and artificial components has led to active biohybrid swimming microsystems with greatly enhanced capabilities and functionalities compared to the individual biological or synthetic components. These characteristics have positioned these cell-like micromotors as promising biomimetic dynamic tools for potential actuation in vivo. Finally, the key challenges and limitations of cell-like micromotors are discussed in the context of expanded future clinical uses and translation to human trials.