Scientists from all around the world are attempting to figure out how to get anti-cancer drugs to the tumors that they are intended to cure.
One approach would be to utilise modified bacteria as “ferries” to convey drugs to tumors via circulation. Researchers at ETH Zurich have successfully regulated certain bacteria such that they may get through the blood vessel wall and infiltrate tumor tissue. The ETH Zurich researchers opted to experiment with bacteria that are inherently magnetic due to the iron oxide particles they contain, lead by Simone Schurle, Professor of Responsive Biomedical Systems. Magnetospirillum bacteria are sensitive to magnetic fields and may be controlled by magnets located outside the body.
Exploiting temporary gaps
In cell cultures and animals, Schurle and her colleagues have shown that adding a rotating magnetic field to the tumor increases the bacteria’s ability to penetrate through the vascular wall near the malignant growth. At the vascular wall, the bacteria are propelled forward in a circular motion by the rotating magnetic field.
A deeper look is necessary to fully understand how the process for passing the vessel wall works: The blood vessel wall is composed of cells and serves as a barrier between the lifeblood and the tumour tissue, which is pervaded by countless tiny blood vessels. Because of the small spaces between these cells, some substances may pass through the vessel wall.
The cells of the vessel wall govern the size of these intercellular gaps, which can be temporarily broad enough to allow bacteria to pass through.
Strong propulsion and high probability
The ETH Zurich researchers demonstrated that pushing bacteria with a rotating magnetic field is efficient for three reasons using tests and computer simulations. For starters, rotating magnetic field propulsion is ten times more powerful than static magnetic field propulsion. The latter simply establishes the course, and the bacteria must proceed on their own.
The second and most important reason is that germs are constantly moving along the vascular wall, propelled by the revolving magnetic field. When compared to other propulsion modes, where the bacteria’s motion is less explorative, this makes them more likely to encounter the gaps that quickly occur between vessel wall cells. Third, unlike previous technologies, imaging is not required to track the microorganisms. The magnetic field does not need to be readjusted once it is placed over the tumor.
“Cargo” accumulates in tumor tissue
“We make use of the bacteria’s natural and autonomous locomotion as well,” Schurle explains. “Once the bacteria have passed through the blood vessel wall and are in the tumor, they can independently migrate deep into its interior.” For this reason, the scientists use 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 tumor.
In the future, such microorganisms could transport anti-cancer medications. The ETH Zurich researchers emulated this application in cell culture studies by attaching liposomes (nanospheres of fat-like substances) to the bacterium. They labelled these liposomes with a fluorescent dye, allowing them to show in a Petri dish that the bacteria had delivered their “cargo” into the malignant tissue, where it accumulated. Liposomes would be loaded with medication for future medicinal use.
Bacterial cancer therapy
One of two ways bacteria can help in the fight against cancer is by acting as medication ferries. The other strategy, which has been around for almost a century, is based on the natural proclivity of specific types of bacteria to harm tumor cells. This could entail a number of processes. In any event, it is known that the bacteria trigger immune system cells, which then kill the tumor.
Several research studies are actively looking into the effectiveness of E. coli bacteria against tumors. Today, microbes can be modified through synthetic biology to improve their medicinal impact, eliminate side effects, and make them safer.
Making non-magnetic bacteria magnetic
However, in order to exploit bacteria’s intrinsic qualities in cancer therapy, the question of how these bacteria can efficiently reach the tumor must be addressed. While it is possible to inject the bacteria directly into tumors at the body’s surface, it is not possible to do so for tumors deep within the body. Professor Schurle’s micro robotic control comes into play here. “We hope our engineering technique can be used to improve the efficacy of bacterial cancer therapy,” she says.
Because E. coli employed in cancer research is not magnetic, it cannot be driven or controlled by a magnetic field. Magnetic responsiveness is a fairly rare feature among microorganisms in general. Magnetospirillum is one of the few bacteria genera with this characteristic.
As a result, Schurle hopes to make E. coli germs magnetic as well. This could one day allow a magnetic field to be utilised to regulate clinically employed medicinal microbes that lack natural magnetism.