Engineers have designed small robots that can help nanoparticles for delivery of drugs to break their way from the bloodstream and tumor or other disease. Magnetic microbials could help to overcome one of the biggest disruptions in the delivery of drugs with nanoparticles: to get out of the blood vessels and to accumulate in the right place.
MIT engineers designed small robots that can help nanoparticles for delivery of drugs to push the bloodstream and tumor or other disease. Like crafts in the movie "Fantastic Voyage" – a science fiction film in the 1960s, in which the submarine accumulated in large quantities and struck the body for the repair of damaged cells – robots swam through the bloodstream, creating a stream that drags the nanoparticles together with them .
Magnetic microrobots, inspired by a bacterial plant, could help to overcome one of the biggest barriers to the delivery of drugs with nanoparticles: getting the particles out of the blood vessels and accumulating in the right place.
"When you put nanomaterials in the bloodstream and direct them to diseased tissue, the biggest barrier to this type of tissue-carrying load is the lining of the blood vessel," says Sandhita Batia, John's professor and Dorothy Wilson of Health Sciences and Technology and Electrical Engineering and Computer Science, a member of the MIT Koch Institute for Integrative Research on Cancer and her Institute of Medical Engineering and Science and senior author of the study.
"Our idea was to see if you can use magnetism to create the fluid forces that push the nanoparticles into tissue," added Simon Shuhrle, a former post-director of MIT and the main author of the paper, which appeared in the April 26 issue Progress in science.
In the same study, the researchers also showed that they could achieve a similar effect using viruses of living bacteria that are naturally magnetic. Each of these approaches could be suitable for different types of drug delivery, researchers say.
Shuhrle, now an assistant professor at the Swiss Federal Institute of Technology (ETH Zurich), first started working on small magnetic robots as a graduate student at Brad Nelson's robotics lab in ETH Zurich. When in 2014 she came to the Batthia Laboratory as a postdox, she began to investigate whether this type of bot could help make nanoparticles delivering drugs more effective.
In most cases, researchers direct their nanoparticles at disease sites surrounded by "leaky" blood vessels, such as tumors. This makes it easier for the particles to enter the tissue, but the delivery process is still not as effective as it should.
The MIT team decided to investigate whether the forces generated by magnetic robots could offer a better way to push the particles out of the bloodstream and reach the target site.
The robots used by Shuhrle in this study are 35 hundredths of a millimeter long, similar in size to one cell, and can be controlled by using an external magnetic field. This bio-intervening robot, which researchers call an "artificial bacterial flag," consists of a small spiral that resembles a flagella that many bacteria use to move. These robots are printed with 3-D printing with a high-resolution 3D 3D printer, then coated with nickel, making them magnetic.
To test the ability of a robot to control nanoparticles in the vicinity, the researchers have created a microfluidic system that mimics the blood vessels surrounding the tumors. The channel in their system, wide from 50 to 200 microns, is arranged with a gel that has holes for simulating broken blood vessels viewed near tumors.
Using external magnets, the researchers applied magnetic fields to the robot, which makes helix rotate and swim through the channel. Since the fluid flows through the channel in the opposite direction, the robot remains motionless and creates a convective current that pushes the 200 nanometer polystyrene particles in the model tissue. These particles penetrated twice as far in the tissue as nanoparticles, without the aid of the magnetic robot.
This type of system can potentially be incorporated into stents that are stationary and easily targeted with an external magnetic field. Such an approach could be useful for delivering drugs to help reduce inflammation at the site of the stent, says Bhathiya.
The researchers also developed a variant of this approach that relies on visits to naturally occurring magneto-toxic bacteria, rather than microbes. Bhatia has previously developed bacteria that can be used to deliver drugs to fight cancer and diagnose cancer, taking advantage of the natural tendency of bacteria to accumulate at disease sites.
For this study, the researchers used a type of bacteria called Magnetospirillum magneticum, which naturally produces chains of iron oxide. These magnetic particles, known as magnetosomes, help the bacteria to orient themselves and find their inclined environments.
The researchers found that when they placed these bacteria in the microfluidic system and applied rotating magnetic fields in certain orientations, the bacteria started to synchronize and move in the same direction, retreating along all the nanoparticles that were nearby. In this case, the researchers found that the nanoparticles were three times faster in the model tissue than when the nanoparticles were delivered without magnetic aid.
This bacterial approach could be better for delivering drugs in situations such as a tumor, where the tongue, controlled externally without the need for visual feedback, can generate fluid fluid in vessels during the tumor.
The particles used by the researchers in this study are large enough to carry large loads, including the components needed for the CRISPR system for regulating the genome, says Bhatia. She now plans to collaborate with Shurlee to further develop both of these magnetic approaches to testing animal models.
The research was funded by the Swiss National Science Foundation, Branko Weiss Fellowship, the National Institute of Health, the National Science Foundation and the Medical Institute, Howard Hughes.