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First demonstration of micromotor operation and payload release in living organism (w/video)
(Nanowerk Spotlight) Synthetic micro- and even nanoscale motors – inspired by the 1966 Fantastic Voyage movie – have been introduced nearly a decade ago. Although major progress has been made toward biomedical applications of these tiny vehicles (see for instance our Nanowerk Spotlights: "Another nanotechnology step towards 'Fantastic Voyage'" and "Micro- and nanomotors powered by water as the sole fuel source"), there are no reports so far illustrating and examining the operation and behavior of nano/microscale motors in living organisms.
Now, a new study addresses the challenges of operating synthetic motors in living organisms through the use of biocompatible motors that are powered by body fluid (acidic stomach environment). As the zinc body of the motor is dissolved by the acid fuel, the motors are self-destroyed, leaving no harmful chemicals behind.
This work, a joint collaborative effort between the teams of Professors Joseph Wang and Liangfang Zhang at the Nanoengineering Department at UCSD, is the first in vivo study of artificial micromotors using a live mouse model.
The study, published in the December 30, 2014 online edition of ACS Nano ("Artificial Micromotors in the Mouse’s Stomach: A Step toward in Vivo Use of Synthetic Motors"), reports on the distribution, retention, cargo delivery and toxicity profile of zinc/polymer-based microrockets in mouse stomach.
Preparation and characterization of PEDOT/Zn micromotors
Preparation and characterization of PEDOT/Zn micromotors. (a) Schematic of the in vivo propulsion and tissue penetration of the zinc-based micromotors in mouse stomach. (b) Preparation of PEDOT/Zn micromotors using polycarbonate membrane templates: (I) deposition of the PEDOT microtube, (II) deposition of the inner zinc layer, and (III) dissolution of the membrane and release of the micromotors. (c) Scanning electron microscopy (SEM) image (left) of the PEDOT/Zn micromotors and the corresponding energy-dispersive X-ray spectroscopy (EDX) data (right) of elemental Zn in the micromotors. Scale bar, 5 µm. (d) Time lapse images (1 s intervals, IIV) of the propulsion of PEDOT/Zn micromotors in gastric acid under physiological temperature (37 C). Scale bar, 20 µm. (Reprinted with permission by American Chemical Society) (click on image to enlarge)
"Our study demonstrates that the self-propulsion of these microrockets leads a dramatically improved retention of their payloads in the stomach lining compared to the common passive diffusion and dispersion of orally administrated payloads," Zhang tells Nanowerk.
"Among the variety of recently developed artificial micromotors, our recently reported zinc-based motors hold great promise for in vivo use, particularly for gastric drug delivery, because of their unique features, including acid-powered propulsion, high loading capacity, autonomous release of payloads, and nontoxic self-destruction," explains Wang.
Using established membrane templating processes, the team's zinc-based micromotors can display efficient propulsion in a harsh acidic environment without additional fuel and transport fully loaded cargoes at high speeds.
In their experiments, the researchers inserted their micromotors, loaded with gold nanoparticles as payload, to the stomach of living mice and then evaluated their autonomous movement in gastric acid and the motion-induced biodistribution and retention of the micromotors on the stomach wall.
"Our results demonstrate that the self-propulsion of the micromotors leads to a dramatically improved retention of their payloads in the stomach lining compared to the common passive diffusion and dispersion of orally administrated payloads," notes Wei Gao, the paper's first author.
The team points out that these findings, along with the absence of toxic effects in stomach, indicate that the movement of micromotors in the stomach fluid offers potentially distinct advantages for in vivo biomedical applications and pave the way for their future clinical studies.
"Our new findings and insights are expected to advance the field of synthetic nano/micromotors and to promote interdisciplinary collaborations towards expanding the horizon of man-made nanomachines in medicine towards the realization of the ‘Fantastic Voyage’ vision," Wang concludes.
Michael Berger By – Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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