Tiny robots recently designed by MIT engineers can aid drug-delivery nanoparticles to navigate their path out of the bloodstream and reach a tumor or other similar sites of disease.
MIT engineers have designed a magnetic microrobot that can help push drug-delivery particles into tumor tissue (left). They also employed swarms of naturally magnetic bacteria to achieve the same effect (right). (Image credit: MIT)
The robots are similar to the crafts seen in “Fantastic Voyage”—a science fiction film that came in the 1960s and in which the crew in a submarine reduces in size and travels throughout a body to heal injured cells. Swimming through the bloodstream, these robots produce a current that helps them to pull the nanoparticles along with them.
Inspired by the propulsion of bacteria, the new magnetic microrobots can help in resolving one of the biggest barriers to delivering drugs with the help of nanoparticles—that is, getting the tiny particles to leave the blood vessels and collect up in the right location.
When you put nanomaterials in the bloodstream and target them to diseased tissue, the biggest barrier to that kind of payload getting into the tissue is the lining of the blood vessel.
Sangeeta Bhatia, Study Senior Author and John and Dorothy Wilson Professor, Departments of Health Sciences and Technology and Electrical Engineering and Computer Science, MIT
Bhatia is a member of MIT’s Koch Institute for Integrative Cancer Research and its Institute for Medical Engineering and Science.
Our idea was to see if you can use magnetism to create fluid forces that push nanoparticles into the tissue.
Simone Schuerle, Study Lead Author and Former MIT Postdoc, Swiss Federal Institute of Technology (ETH Zurich)
The study has been reported in the April 26
th, 2019 issue of Science Advances.
In the same research, the investigators also demonstrated that a similar effect could be obtained by utilizing hordes of living and naturally magnetic bacteria. According to the researchers, all these methods can possibly be used for various kinds of drug delivery.
When Schuerle was a graduate student in Brad Nelson’s Multiscale Robotics Lab at ETH Zurich, she initially started to work on very small magnetic robots. Later, when she came to Bhatia’s lab as a postdoc in 2014, she started to explore whether this kind of robot could aid in delivering the nanoparticles more efficiently. At present, Schuerle is an assistant professor at the Swiss Federal Institute of Technology.
In a majority of cases, nanoparticles are usually targeted to disease sites that are covered by “leaky” blood vessels, like tumors. While this renders it easier for the nanoparticles to penetrate into the tissue, the process of delivery was still not as effective as it had to be.
Therefore, the MIT researchers decided to investigate whether the forces produced by magnetic robots could provide a more improved method to force the nanoparticles out of the bloodstream and make them reach the target site.
For the study, Schuerle employed 35 robots that measure hundredths of a millimeter in length and resemble the size of one cell. An external magnetic field can be applied to control these robots. The bioinspired robot, dubbed “artificial bacterial flagellum,” by the researchers, includes a small helix that looks like the flagella used by a number of bacteria to propel themselves. A high-resolution 3D printer is used to 3D print these robots and then nickel is used to coat them and thus make them magnetic.
In order to test the potential of a single robot in controlling the neighboring nanoparticles, the scientists produced a microfluidic system that imitates the blood vessels surrounding tumors. The channel within their system, measuring 50 to 200 µm wide, is coated with a gel that contains holes to replicate the broken blood vessels observed close to the tumors.
The researchers then used external magnets to apply magnetic fields to the robot, which causes the helix to revolve and swim across the channel. Since fluid flows via the channel in the reverse direction, the magnetic robot continues to be immobile and produces a convection current, which, in turn, forces 200-nm polystyrene particles inside the model tissue. Such particles were able to penetrate twice as deep into the tissue as nanoparticles were delivered without the help of the magnetic robot.
Such a system can possibly be integrated into stents, which are immobile and can be easily targeted by applying a magnetic field externally. According to Bhatia, this method can be viable for delivering drugs to help decrease inflammation at the stent’s site.
A variant of this method was also developed by the team. This method depends on groups of naturally magnetotactic bacteria rather than microrobots. Earlier, Bhatia had created bacteria that can be used to diagnose cancer and to deliver drugs that fight cancer, leveraging the natural tendency of the bacteria to collect at the sites of disease.
In this work, a type of bacteria known as
Magnetospirillum magneticum was used by the researchers. The bacteria naturally create iron oxide chains, and these magnetic particles, called magnetosomes, help the microbes to orient themselves and locate their required environments.
The team observed that when they these bacteria are placed inside the microfluidic system and then rotating magnetic fields are applied in specific orientations, the microorganisms started to rotate in synchrony and travel in the same direction, dragging any nearby nanoparticles along with them. In such a case, the scientists observed that compared to the nanoparticles delivered without any magnetic assistance, those nanoparticles were pushed inside the model tissue three times faster.
This novel bacterial method would be more suitable to deliver drugs in cases, like a tumor, wherein the swarm of living bacteria, regulated externally without the necessity for visual feedback, may create fluidic forces in vessels all through the tumor.
Bhatia stated that the nanoparticles utilized by the investigators in this analysis are sufficiently large to carry bulk payloads, including the components needed for the CRISPR genome-editing system. Currently, she is planning to team up with Schuerle to further advance the two magnetic methods for testing in animal models.
The Swiss National Science Foundation, the National Institutes of Health, the Branco Weiss Fellowship, the National Science Foundation, and the Howard Hughes Medical Institute funded the study.