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Tiny robots powered by magnetic fields could help nanoparticles deliver their drug targets



  Tiny robots driven by magnetic fields could help nanoparticles deliver drug targets
A vision of improved transport of nanomedicine into tumor tissue. Picture credits: Sonia Monti

MIT engineers have developed tiny robots that can help deliver nanoparticles from the bloodstream to a tumor or other disease site for drug delivery. Like the craft of "Fantastic Voyage" ̵

1; a science fiction movie from the 1960s, in which a submarine crew shrinks in size to repair damaged cells – the robots swim through the bloodstream creating a flow entraining the nanoparticles.

The magnetic microrobots excited by bacterial drives could help overcome one of the biggest barriers to drug delivery with nanoparticles: the particles are induced to leave blood vessels and accumulate in the right place.

The bloodstream and its target for diseased tissue, the biggest obstacle to this type of payload that invades tissue, is the lining of the blood vessel, "says Sangeeta Bhatia, Professor of Health Sciences, Technology, Electrical, and Computer from John and Dorothy Wilson Science, member of MIT's Integrative Cancer Research Institute and Institute of Medical Engineering and Science, and lead author of the study.

"Our idea was to use magnetism to create fluid forces that force nanoparticles into the tissue, "adds Simone Schuerle, a former MIT postdoc and lead author of the newspaper, which appears in the April 26 issue Science Advances [19459]. 015].

In the same study, the researchers showed also that they can achieve a similar effect with swarms of living bacteria that are magnetic in nature. that each of these approaches could be suitable for different types of drug delivery.




Magnetically controlled synthetic and living microprocessors stir up nanoparticles for improved drug delivery. Picture credits: Schuerle et al., Sci. Adv. 2019; 5: eaav4803

Tiny Robots

Schuerle, who is now Assistant Professor at ETH, began his career as a small student at Brad Nelson's Multiscale Robotics Lab at ETH Zurich. When she came to Bhatia's lab in 2014 as a postdoctoral researcher, she began to investigate whether this type of bot could help to make the drug delivery of nanoparticles more efficient.

In most cases, researchers direct their nanoparticles to disease centers that "leak" "blood vessels, such as tumors, making it easier for the particles to enter the tissues, but the delivery process is still not as effective as it is

The MIT team decided to investigate whether the forces generated by magnetic robots could provide a better route Slide the particles out of the bloodstream to the target site.

The robots used by Schuerle in this study are 35 hundredths of a millimeter long, resemble a single cell and can be controlled by applying an external magnetic field.This bioinspired robot, which the researchers call "artificial bacterial flagellum", consists of a tiny helix that resembles the flagella that many bacteria use to drive printed with a high-resolution 3D printer in 3D and then coated with nickel to make them magnetic

To test the ability of a single robot to control nanoparticles nearby, researchers developed a microfluidic system that mimics the blood vessels surrounding tumors. The channel, between 50 and 200 microns wide, is lined with a gel that has holes to simulate broken blood vessels near tumors.

<img src = "https://3c1703fe8d.site.internapcdn.net/newman/csz/news/800/2019/5cc34371bad12.jpg" alt = "Tiny robots powered by magnetic fields could help Drug Nanoparticles Achieve Their Goals [19659016] Detection of synthetic micropropagators in tumor tissue by multi-photon imaging and second Harmoincs signals Photo credits: Jeffrey Wyckoff

Using external magnets, the researchers applied magnetic fields to the robot, causing the helix to rotate and float through the channel. As the liquid flows in the opposite direction through the channel, the robot stops and creates a convection current that pushes 200 nanometer polystyrene particles into the model fabric. These particles penetrated the tissue twice as much as nanoparticles released without the help of the magnetic robot.

This type of system could potentially be incorporated into stationary stents and would be easy to aim with an externally applied magnetic field. Such an approach could be helpful in delivering medication to reduce inflammation at the site of the stent, says Bhatia.

Bacterial Swarms

The researchers also developed a variant of this approach based on swarms of naturally magnetotactic bacteria rather than microrobots. Bhatia has already developed bacteria that can be used to deliver anticancer medicines and diagnose cancer to exploit the natural tendency of bacteria to accumulate at the disease sites.

For this study, researchers used a type of bacteria called Magnetospirillum magneticum, which naturally occurs producing chains of iron oxide. These magnetic particles, called magnetosomes, help bacteria to orient themselves and find their preferred environments.

The researchers discovered that if they introduced these bacteria into the microfluidic system and applied rotating magnetic fields in certain orientations, the bacteria would spin synchronously and move in the same direction, pulling all the nanoparticles that are nearby , In this case, the researchers found that nanoparticles were pushed three times faster into the model tissue than if the nanoparticles were delivered without magnetic support.

This bacterial approach may be more appropriate for drug delivery in situations such as a tumor where possible. The externally controlled swarm without visual feedback could create fluidic forces in vessels throughout the tumor.

The particles used by the researchers in this study are large enough to transport large payloads, including the component-editing system required for the CRISPR genome, Bhatia says. She is now planning to collaborate with Schuerle to develop these two magnetic approaches to animal testing.


Microrobots that can form different types of swarm forms


Further information:
"Synthetic and Living Micropropellers for the Transport of Convection-Enhanced Nanoparticles" Science Advances (2019). advances.sciencemag.org/content/5/4/eaav4803

Provided by
Massachusetts Institute of Technology




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Tiny Robots Powered by Magnetic Fields May Help to Deliver Drug Nanoparticles (2019, April 26)
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