Biotechnology

Fighting cancer with magnetic bacteria

Magnetic bacteria (gray) can squeeze through narrow intercellular spaces, cross the wall of blood vessels and penetrate tumors. Author: Yimo Yan / ETH Zurich

Researchers are working to determine the best way for anticancer drugs to reach the tumors they are meant to treat. One option is to use modified bacteria as “ferries” to transport drugs to tumors via the bloodstream. ETH Zurich Researchers have now successfully controlled some bacteria so that they can pass through the wall of blood vessels and enter tumor tissue.

ETH Zurich researchers led by Simone Schürle, professor of reactive biomedical systems, decided to experiment with bacteria that are inherently magnetic thanks to the iron oxide particles they contain. These Magnetospirilla bacteria respond to magnetic fields and can be manipulated by external magnets.

Use of temporary gaps

Schuerle and her colleagues have now shown in cell cultures and mice that applying a rotating magnetic field to a tumor increases the bacteria’s ability to cross the vascular wall around a cancerous tumor. The rotating magnetic field moves the bacteria in a circular motion along the vascular wall.

To better understand the mechanism of crossing the vessel wall, it is necessary to consider in detail: The wall of a blood vessel consists of a layer of cells and serves as a barrier between blood flow and tumor tissue, which is permeated with many small blood vessels. The 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 wide enough to allow even bacteria to pass through the vessel wall.

Strong movement and high probability

Using experiments and computer simulations, ETH Zurich researchers were able to show that moving bacteria using a rotating magnetic field is effective for three reasons. First, motion by a rotating magnetic field is ten times more powerful than motion by a static magnetic field. The latter only sets the direction, and the bacteria must move under their own power.

The second and most important reason is that the bacteria moved by the rotating magnetic field are constantly moving, moving along the vessel wall. This makes them more likely to encounter gaps that briefly open between the cells of the vessel wall compared to other types of motors, in which bacterial movement is less exploratory. And third, unlike other methods, bacteria do not need to be tracked using imaging. If the magnetic field is placed over the tumor, it does not need to be adjusted.

“Cargo” accumulates in the tumor tissue

“We also use the natural and autonomous movement of bacteria,” Schürle explains. “Once the bacteria have passed through the wall of the blood vessel and found themselves in the tumor, they can independently migrate deep into its interior.” For this reason, scientists use movement with an external magnetic field for just one hour – long enough for the bacteria to effectively pass through the vascular wall and reach the tumor.

Such bacteria may in the future tolerate anti-cancer drugs. In their cell culture studies, ETH Zurich researchers modeled this application by attaching liposomes (nanospheres of fat-like substances) to bacteria. They labeled these liposomes with a fluorescent dye, which allowed them to demonstrate in a petri dish that the bacteria had indeed delivered their “cargo” to the cancerous tissue, where it accumulated. In future medical applications, liposomes will be loaded with drugs.

Treatment of bacterial cancer

Using bacteria as a drug ferry is one of two ways bacteria can help fight cancer. Another approach is more than a hundred years old and is now experiencing a renaissance: exploiting the natural tendency of certain types of bacteria to damage tumor cells. This may involve several mechanisms. In any case, it is known that bacteria stimulate certain cells of the immune system, which then eliminate the tumor.

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

We make non-magnetic bacteria magnetic

However, in order to use the intrinsic properties of bacteria in cancer therapy, the question remains as to how these bacteria can effectively reach the tumor. Although it is possible to inject bacteria directly into tumors near the surface of the body, this is not possible for tumors deep inside the body. This is where Professor Schuerle’s micro-robotic control comes into play. “We think we can use our engineering approach to improve the effectiveness of bacterial cancer therapy,” she says.

Escherichia coli used in cancer research is not magnetic and therefore cannot be driven and controlled by a magnetic field. In general, magnetic sensitivity is a very rare phenomenon among bacteria. Magnetospirilla is one of the few genera of bacteria that possess this property.

Therefore, Schürle wants to make the E. coli bacteria also magnetic. This may one day make it possible to use a magnetic field to control clinically used therapeutic bacteria that lack natural magnetism.

Reference: “Living Microrobots Driven by Magnetic Torque to Augment Tumor Infiltration” by T. Gwisai, N. Mirkani, MG Christiansen, TT Nguyen, V. Ling, and S. Schurrle, 26 October 2022. Scientific robotics.
DOI: 10.1126/scirobotics.abo0665



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