Use of magnetic bacteria to combat cancerous tumors

Use of magnetic bacteria to combat cancerous tumors

Researchers at ETH Zurich want to use magnetic bacteria to combat cancerous tumors. They have now found a way in which these microorganisms can effectively cross blood vessel walls and then colonize a tumor.

Scientists around the world are researching how cancer drugs can most efficiently reach the tumors they target. One possibility is to use modified bacteria as “ferries” to transport the drugs to the tumors via the bloodstream. Researchers at ETH Zurich have now succeeded in controlling certain bacteria so that they can effectively overcome the blood vessel wall and penetrate tumor tissue.

Led by Simone Schürle, Professor of Responsive Biomedical Systems, the ETH researchers decided to work with bacteria that are naturally magnetic due to the iron oxide particles they contain. These bacteria of the genus Magnetospirillum respond to magnetic fields and can be controlled by magnets from outside the body; more about this in an earlier article in ETH News [ https://ethz.ch/en/news-and-events/eth-news/news/2020/12/magnetic-bacteria-as-micropumps.html ].

Exploit temporary gaps

In cell cultures and on mice, Schürle and her team have now been able to show that a rotating magnetic field applied to the tumor improves the bacteria's ability to cross the vessel wall near the cancerous tumor. The rotating magnetic field drives the bacteria forward in a circle on the vessel wall.

In order to better understand the mechanism for crossing the vessel wall, a closer look is necessary: ​​The blood vessel wall consists of a layer of cells and serves as a barrier between the bloodstream and the tumor tissue, which is permeated by many small blood vessels. Narrow spaces between these cells allow certain molecules to pass through the vessel wall. The size of these intercellular spaces is regulated by the cells of the vessel wall and they can temporarily be so large that even bacteria can pass through the vessel wall.

Strong propulsion and high probability

With the help of experiments and computer simulations, the ETH researchers were able to show that propelling bacteria using a rotating magnetic field is effective for three reasons. First, propulsion via a rotating magnetic field is ten times stronger than propulsion via a static magnetic field. The latter simply sets the direction and the bacteria have to move under their own power.

The second and most important reason is that bacteria, driven by the rotating magnetic field, are constantly moving and migrating along the vessel wall. As a result, they are more likely to encounter the gaps that briefly open between vessel wall cells than with other types of propulsion in which the bacteria move less exploratively. And thirdly, unlike other methods, the bacteria do not need to be tracked using imaging. Once the magnetic field is positioned over the tumor, it no longer needs to be readjusted.

“Cargo” accumulates in tumor tissue

We also take advantage of the bacteria’s natural and autonomous movement. As soon as the bacteria have passed through the blood vessel wall and are in the tumor, they can independently migrate deep into its interior.”

Simone Schürle, Professor of Responsive Biomedical Systems, ETH Zurich

For this reason, the scientists use the drive from the external magnetic field for only one hour - long enough for the bacteria to efficiently pass through the vessel wall and reach the tumor.

Such bacteria could transport drugs against cancer in the future. In their cell culture studies, the ETH researchers simulated this application by attaching liposomes (nanospheres made of fat-like substances) to the bacteria. They labeled these liposomes with a fluorescent dye that allowed them to demonstrate in the Petri dish that the bacteria had actually delivered their “cargo” into the cancer tissue, where they accumulated. In a future medical application, the liposomes would be filled with a drug.

Bacterial cancer therapy

Using bacteria as ferries for drugs is one of two ways bacteria can help in the fight against cancer. The other approach is over a hundred years old and is currently experiencing a revival: exploiting the natural tendency of certain types of bacteria to damage tumor cells. This can involve several mechanisms. What is known is that the bacteria stimulate certain cells of the immune system, which then eliminate the tumor.

Several research projects are currently investigating the effectiveness of E. coli bacteria against tumors. Today it is possible to modify bacteria using synthetic biology to optimize their therapeutic effects, reduce side effects and make them safer.

Making non-magnetic bacteria magnetic

But in order to utilize the inherent properties of bacteria in cancer therapy, the question remains as to how these bacteria can efficiently reach the tumor. While it is possible to inject the bacteria directly into tumors near the surface of the body, this is not possible with tumors deep in the body. This is where Professor Schürle’s microrobot controller comes into play. “We believe that with our technical approach we can increase the effectiveness of bacterial cancer therapy,” she says.

E. coli, which was used in the cancer studies, is not magnetic and therefore cannot be powered and controlled by a magnetic field. In general, magnetic responsiveness is a very rare phenomenon in bacteria. Magnetospirillum is one of the few bacterial genera that possess this property.

Schürle therefore also wants to make E. coli bacteria magnetic. This could one day make it possible to control clinically used therapeutic bacteria that do not have natural magnetism using a magnetic field.

Source:

ETH Zurich

Reference:

Gwisai, T., et al. (2022) Magnetic torque-driven living microrobots for increased tumor infiltration. Scientific robotics. doi.org/10.1126/scirobotics.abo0665.

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