Chemically Propelled Nano and Micromotors in the Body: Quo Vadis?

Abstract

The active delivery of drugs to disease sites in response to specific biomarkers is a holy grail in theranostics. If successful, it would greatly diminish the therapeutic dosage and reduce collateral cytotoxicity. In this context, the development of nano and micromotors that are able to harvest local energy to move directionally is an important breakthrough. However, serious hurdles remain before such active systems can be employed in vivo in therapeutic applications. Such motors and their energy sources must be safe and biocompatible, they should be able to move through complex body fluids, and have the ability to reach specific cellular targets. Given the complexity in the design and deployment of nano and micromotors, it is also critically important to show that they are significantly superior to inactive “smart” nanoparticles in theranostics. Furthermore, receiving regulatory approval requires the ability to scale‐up the production of nano and micromotors with uniformity in structure, function, and activity. In this essay, the limitations of the current nano and micromotors and the issues that need to be resolved before such motors are likely to find theranostic applications are discussed.

Relative Diffusivities of Bound and Unbound Protein Can Control Chemotactic Directionality

“…Recent studies have shown that ensembles of single enzyme molecules, − as well as enzyme-attached microparticles, − also chemotax in response to a gradient of the substrate. This phenomenon has been exploited to direct the motion of enzymes and enzyme-attached particles to specific locations in space, e.g., for drug delivery applications. − Despite the importance of the phenomenon and the myriad of applications that stem from it, the mechanistic basis of chemotaxis in synthetic systems remains poorly understood. For example, it has been suggested that chemotaxis requires that the motile particles possess an active coupling of their orientation to the chemical gradient .…”

Navigation of Ultrasound-controlled Swarmbots under Physiological Flow Conditions

“…Recent research has tended to exploit the motion of synthetic swimmers near boundaries, where non-slip conditions minimize flow velocity, drag force is reduced, and upstream manipulation is easier. Catalytic approaches have been widely investigated (17)(18)(19)(20)(21)(22), and Katuri et al demonstrated a controlled crossstream motion of janus particles, which could mimic the motion of natural microswimmers and be exploited to reach vessel boundaries (23). Importantly, some approaches have already managed to manipulate microswimmers upstream when they are close to a wall.…”

Fluorescence Detection of miRNA-21 Using Au/Pt Bimetallic Tubular Micromotors Driven by Chemical and Surface Acoustic Wave Forces

“…1−7 In comparison to conventional nanocarriers, the nano/micromotors offer several advantages for cell internalization, including enhanced adhesion, better penetration, and a shorter and controllable transporting time based on the propelling mechanism. 8−12 Early studies in the synthesis and application of nano/micromotors focused only on designs based on micromotor motions powered by magnetic, 13 ultrasound, 14−16 and chemical propulsion mechanisms 17,18 and their combinations. 19,20 Chemical propulsion is fast motion, but fuels can have a toxic effect, which limits biological applications.…”

“…Artificial micro- and nanomotors have fascinating capability to move autonomously or under different external energy sources. These molecular machines play an important role in the development of medical applications including active drug delivery, fast detection of tumor markers, and payload transport into cells. − In comparison to conventional nanocarriers, the nano/micromotors offer several advantages for cell internalization, including enhanced adhesion, better penetration, and a shorter and controllable transporting time based on the propelling mechanism. − Early studies in the synthesis and application of nano/micromotors focused only on designs based on micromotor motions powered by magnetic, ultrasound, − and chemical propulsion mechanisms , and their combinations. , Chemical propulsion is fast motion, but fuels can have a toxic effect, which limits biological applications. Unlike chemical propulsion, acoustic propulsion especially offers a unique opportunity to use such microscale devices in biological applications because of its non-toxic fuel requirement, tunability, and prolonged operation time .…”