The idea sounds like something out of a science-fiction novel: Tiny medical machines zooming around the body delivering drugs, taking tissue samples, or performing small surgical repairs. But, now, for the first time, researchers have demonstrated a simple micromotor that can propel itself inside the body (ACS Nano 2014, DOI: 10.1021/nn507097k). When introduced into a mouse’s stomach, the micromotor swims to the stomach lining and delivers cargo.
The study is an important landmark, says Thomas E. Mallouk, who develops nanomotors and micromotors at Pennsylvania State University. It shows the potential of motorized particles to possibly improve the functions of nanoparticle drug carriers and imaging agents.
In recent years, researchers have designed microsized motors that react with chemicals around them in solution to produce jets of bubbles, propelling them forward or actuating moving parts. These particles can swim or perform tasks, such as sorting cells in tubes of blood. But so far, no one had tested the devices inside an animal. Joseph Wang, a nanoengineer at the University of California, San Diego, says one major challenge has been the fuel that the motors react with to zip around. For example, his early designs used toxic hydrogen peroxide. Wang and others in the field want to design new motors that can use chemicals found in an organism as fuel, without producing toxic by-products.
In 2012, Wang and his colleagues made micromotors fueled by acids, which offered the potential to run the devices on bodily fluids, such as gastric juices (J. Am. Chem. Soc., DOI: 10.1021/ja210874s). The motors consist of 20-μm-long, 5-μm-wide cylindrical tubes of the biocompatible polymer poly(3,4-ethylenedioxythiophene), or PEDOT, filled with zinc. The zinc reduces hydrogen ions to produce bubbles of hydrogen gas. The tubes can reach speeds of about 60 μm per second.
In the new study, Wang worked with Liangfang Zhang, a nanomedicine researcher at UCSD, to test the ability of these micromotors to deliver cargo to the stomach walls of mice. They thought that, unlike passive particles, jet-propelled ones could penetrate the thick layer of mucus that lines the stomach and then remain embedded until they dissolved.
The team first compared the micromotors with ones that were filled with platinum, which doesn’t react with acid to form propellant bubbles, instead of zinc. The researchers used a tube to deliver precise doses of the two particle types into the stomachs of mice. After two hours, nearly four times as many zinc micromotors as platinum particles remained in the stomach tissue, suggesting that the jet-propelled motors could penetrate that thick mucus layer.
Next, the researchers tested the micromotors’ ability to deliver cargo in the form of gold nanoparticles. When mice received an oral dose of micromotors whose polymer coat was embedded with gold nanoparticles, the animals ended up with 168 ng of gold per gram of stomach tissue after two hours; those given an equivalent dose of gold nanoparticles alone had 53.6 ng/g. These results, the researchers say, show that loading cargo in micromotors can improve the efficiency of delivery.
Also the team saw no signs of toxicity or immune reactions from the micromotors in the mice. Inside the stomachs, the micromotors completely dissolved without generating toxic by-products.
The UCSD team plans to build on these early results by adding more functionality to their particles. “We’re trying to add grippers that will move in response to changes in pH,” Wang says.