Magnetic bacteria are being developed by researchers to combat cancerous tumors. They have now discovered a method for these microorganisms to cross blood vessel walls and colonize a tumor.
Scientists all over the world are working to figure out how to get anti-cancer drugs to the tumors they’re meant to treat. One possibility is to use modified bacteria as “ferries” to transport drugs through the bloodstream to tumors. Researchers at ETH Zurich have now successfully controlled certain bacteria so that they can cross the blood vessel wall and infiltrate tumor tissue.
The ETH Zurich researchers, led by Simone Schürle, Professor of Responsive Biomedical Systems, chose to work with bacteria that are naturally magnetic due to the iron oxide particles they contain. Magnetospirillum bacteria respond to magnetic fields and can be controlled by magnets placed outside the body.
We make use of the bacteria’s natural and autonomous locomotion as well. Once the bacteria have passed through the blood vessel wall and are in the tumour, they can independently migrate deep into its interior.
Simone Schürle
Exploiting temporary gaps
In cell cultures and in mice, Schürle and her team have now shown that a rotating magnetic field applied at the tumour improves the bacteria’s ability to cross the vascular wall near the cancerous growth. At the vascular wall, the rotating magnetic field propels the bacteria forward in a circular motion.
To better understand the mechanism to cross the vessel wall works, a detailed look is necessary: The blood vessel wall consists of a layer of cells and serves as a barrier between the bloodstream and the tumour tissue, which is permeated by many small blood vessels. Narrow spaces between these cells allow certain molecules from the to pass through the vessel wall. How large these intercellular spaces are is regulated by the cells of the vessel wall, and they can be temporarily wide enough to allow even bacteria to pass through the vessel wall.
Strong propulsion and high probability
The ETH Zurich researchers demonstrated, through experiments and computer simulations, that propelling bacteria with a rotating magnetic field is effective for three reasons. For starters, propulsion via a rotating magnetic field is ten times more powerful than propulsion via a static magnetic field. The latter merely sets the course, and the bacteria must move on their own.
The second and most important reason is that bacteria driven by the rotating magnetic field are constantly in motion, traveling along the vascular wall. This makes them more likely to encounter the gaps that briefly open between vessel wall cells than other propulsion types, in which the bacteria’s motion is less explorative. And third, unlike other methods, the bacteria do not need to be tracked via imaging. Once the magnetic field is positioned over the tumour, it does not need to be readjusted.
“Cargo” accumulates in tumour tissue
“We make use of the bacteria’s natural and autonomous locomotion as well,” Schürle explains. “Once the bacteria have passed through the blood vessel wall and are in the tumour, they can independently migrate deep into its interior.” For this reason, the scientists use the propulsion via the external magnetic field for just one hour – long enough for the bacteria to efficiently pass through the vascular wall and reach the tumour.
Such bacteria could carry anti-cancer drugs in the future. In their cell culture studies, the ETH Zurich researchers simulated this application by attaching liposomes (nanospheres of fat-like substances) to the bacteria. They tagged these liposomes with a fluorescent dye, which allowed them to demonstrate in the Petri dish that the bacteria had indeed delivered their “cargo” inside the cancerous tissue, where it accumulated. In a future medical application, the liposomes would be filled with a drug.
Bacterial cancer therapy
One of two ways bacteria can help in the fight against cancer is by acting as drug ferries. The other approach, which has been around for over a century, is based on the natural proclivity of certain species of bacteria to damage tumor cells. This could involve a number of mechanisms. In any case, it is known that the bacteria stimulate immune system cells, which then eliminate the tumor.
Several research projects are currently looking into the effectiveness of E. coli bacteria against tumors. Today, bacteria can be modified using synthetic biology to improve their therapeutic effect, reduce side effects, and make them safer.
Making non-magnetic bacteria magnetic
Yet to use the inherent properties of bacteria in cancer therapy, the question of how these bacteria can reach the tumour efficiently still remains. While it is possible to inject the bacteria directly into tumours near the surface of the body, this is not possible for tumours deep inside the body. That is where Professor Schürle’s microrobotic control comes in. “We believe we can use our engineering approach to increase the efficacy of bacterial cancer therapy,” she says.
Because E. coli used in cancer research is not magnetic, it cannot be propelled or controlled by a magnetic field. Magnetic responsiveness is a very rare phenomenon among bacteria in general. Magnetospirillum is one of the few bacteria genera with this property.
As a result, Schürle hopes to make E. coli bacteria magnetic as well. This could one day allow a magnetic field to be used to control clinically used therapeutic bacteria that lack natural magnetism.
