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Nanoparticles take a fantastic, magnetic flight

April 27, 2019

(Nanowerk News) MIT engineers have developed small robots that can help drug delivery nanoparticles squeeze out the path from the bloodstream and the tumor or other disease site. Like Fantastic Voyage Crafts – a 1960s science fiction film in which the underwater crew shrinks and exits the body to repair damaged cells – robots fly through the bloodstream, creating a current that drives nanoparticles along with them.

Magnetic microbobots inspired by bacterial motility could help overcome one of the biggest obstacles to delivering drugs with nanoparticles: getting particles out of the blood vessels and accumulating in the right place.

"When you put nanomaterials into the bloodstream and target the affected tissues, the biggest obstacle to getting this kind of cargo into the tissues is the blood vessel lining," says Sangeeta Bhatia, Professor of Health Sciences and Computer and Electronics and Computer Science, member of MIT Koch Integrated Cancer Research Institute and its members. Institute of Medical Engineering and Science, as well as senior research author.

"Our idea was to find out if you can use magnetism to create liquid forces that cause nanoparticles to tissue," adds Simone Schuerle, a former MIT postdoc and leading author who appears Science Development ("Robotically Controlled Micropar to Solve Initial Attack Modes Before Phagocytosis").Magnetic microrobot that can help to push drug delivery particles into tumor tissueMIT engineers have developed a magnetic microrobot that can help to push drug delivery particles into tumor tissue (left). They also used natural magnetic traps to achieve the same effect (right). (Image courtesy of researchers) (click image to enlarge)

In the same study, the researchers also showed that they can achieve a similar effect using naturally occurring bacteria. Each of these approaches could be suitable for different types of drug delivery.

Tiny robots

Schuerle, now a associate professor at the Swiss Federal Institute of Technology (ETH Zurich), first started working on a small magnetic robot as a graduate at Brad Nelson Multiscale Robot Laboratory ETH Zurich. When she arrived at the Bhatia Laboratory as a postdocument in 2014, she began to investigate whether such a bot could help improve the delivery of nanoparticles.

In most cases, researchers turn to nanoparticles to the disease sites surrounded by blood vessels such as tumors. This facilitates the penetration of particles into tissues, but the delivery process is still not as effective as needed.

The MIT team decided to investigate whether the forces generated by magnetic robots could offer a better way to squeeze particles out of the bloodstream and target.

The robots used by Schuerle in this study are 35 centimeters long, similar to one cell, and can be controlled using an external magnetic field. This bio-spotted robot, called researchers' flagellum of artificial bacteria, consists of a small spiral similar to the flag used by many bacteria to direct themselves. These robots are 3-D printed with a high-resolution 3-D printer and then coated with nickel that makes them magnetic.

To test the ability of a single robot to control nearby nanoparticles, researchers developed a microfluidic system that mimics blood vessels that surround tumors. In its system, a channel from 50 to 200 microns is lined with a gel containing holes to simulate damaged blood vessels visible to the tumors.

Using external magnets, the researchers used the robotic magnetic fields that rotate the spiral and swim through the channel. As the fluid flows through the channel in the opposite direction, the robot remains stationary and generates convection current that encourages 200 nanometer polystyrene particles on the tissue of the model. These particles penetrated twice as far into the tissue as the nanoparticles supplied without the magnetic robot.

This type of system could be embedded in stents that are stationary and easily positioned with an externally applied magnetic field. Such an approach might be helpful in delivering drugs that help reduce inflammation in the stent site, Bhatia says.

Bacterial feed

The researchers also developed a variant of this approach based on naturally magnetotactic bacterial fungi rather than microbobot. Bhatia has previously developed bacteria that can be used to deliver anticancer drugs and diagnose cancer using the natural tendency of bacteria to accumulate in disease sites.

In this study, researchers used bacteria called Magnetospirillum magneticum, which naturally produce iron oxide chains. These magnetic particles, known as magnetosomes, help the bacteria to navigate and find the desired environment.

The researchers found that by placing these bacteria in the microfluidic system and using rotating magnetic fields in certain directions, the bacteria began to synchronize and move in the same direction by pulling all the nearby nanoparticles. In this case, the researchers found that nanoparticles were inserted into the tissue of the model three times faster than when the nanoparticles were supplied without magnetic aid.

This bacterial approach could be better suited for drug administration in situations such as a tumor, where the gloss externally controlled without visual feedback can produce fluid forces in blood vessels throughout the tumor.

The particles that researchers used in this study are large enough to carry large loads, including the components needed for the CRISPR genome editing system, Bhatia says. Now she plans to work with Schuerle to further develop both of these magnetic approaches for testing animal models.

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