Researchers are working to determine the best way for anti-cancer medications to get to the tumors they are intended to treat. One option is to use altered bacteria as “ferries” to transport the medications to the tumors through the bloodstream. Researchers at ETH Zurich have now successfully managed to prevent some germs from successfully infiltrating tumor tissue by allowing them to pass blood vessel walls.
The ETH Zurich researchers chose to experiment with bacteria that are inherently magnetic due to iron oxide particles they contain, under the direction of Simone Schürle, Professor of Responsive Biomedical Systems. These Magnetospirillum bacteria respond to magnetic fields and can be manipulated by external magnets.
Exploiting temporary gaps
Schürle and her team have now demonstrated in cell cultures and in mice that a rotating magnetic field placed near the tumor enhances the bacteria’s capacity to pass the vascular wall close to the malignant development. The circulating magnetic field at the vascular wall drives the bacteria ahead in a circular motion.
A thorough examination is required to better comprehend how the mechanism to cross the vessel wall functions: Between the bloodstream and the cancer tissue, which is infiltrated by numerous tiny blood vessels, the blood vessel wall, which is made up of a layer of cells, acts as a barrier. Some molecules from the may flow through the vessel wall because of the small openings between these cells. The cells that make up the vessel wall control the size of these intercellular spaces, which can occasionally be large enough to let even bacteria pass through the vessel wall.
High probability and powerful propulsion
The ETH Zurich researchers were able to demonstrate that moving the bacteria using a rotating magnetic field is successful for three reasons with the use of experiments and computer simulations. First, magnetic propulsion using a rotating field is 10 times more effective than magnetic propulsion using a static field. The former only provides the direction; the germs are left to propel themselves.
The second and most important factor is that germs are constantly moving along the vascular wall due to the rotating magnetic field. In contrast to other propulsion modes, where the bacteria’s motion is less explorative, this increases the likelihood that they will come across the gaps that momentarily appear between vessel wall cells. Thirdly, unlike previous approaches, imaging is not required to follow the microorganisms. It is not necessary to reposition the magnetic field once it has been placed over the tumor.
‘Cargo’ builds up in tumor tissue.
Schürle says, “We also use the inherent and autonomous motility of the bacteria.” “The bacteria can independently travel deep into the tumor’s interior once they have passed through the blood vessel wall.” For this reason, the researchers only employ the external magnetic field’s propulsion for an hour, which is just long enough for the bacteria to successfully penetrate the vascular wall and reach the tumor.
In the future, these microorganisms might transport anti-cancer medications. The ETH Zurich researchers mimicked this application in their cell culture investigations by affixing liposomes—nanospheres made of molecules that resemble fat—to the bacterium. In order to show in the Petri dish that the bacteria had truly transported their “cargo” into the malignant tissue, where it gathered, they labeled these liposomes with a fluorescent dye. In a future medicinal use, a medicine would be contained within liposomes.
Bacterial cancer therapy
One of the two ways that bacteria can aid in the fight against cancer is by acting as ferries for medications. The other strategy dates back more than a century and is currently enjoying a resurgence: harnessing specific bacterial species’ innate predisposition to harm tumor cells. Multiple mechanisms might be involved in this. In any event, it is well known that particular immune system cells are stimulated by the bacteria and then destroy the tumor.
The effectiveness of E. coli bacteria against tumors is currently the subject of numerous research efforts. Using synthetic biology, it is now possible to alter microorganisms to improve their medicinal impact, lessen their adverse effects, and make them safer.
Making non-magnetic bacteria magnetic
The issue of how these bacteria can effectively reach the tumor still needs to be resolved before using the intrinsic qualities of bacteria in cancer therapy. Although it is possible to inject the bacteria directly into tumors that are close to the body’s surface, this is not an option for tumors that are deeply buried. Microrobotic control by Professor Schürle enters the picture here. We think our engineering strategy will improve the effectiveness of bacterial cancer therapy, she adds.
Because E. coli employed in the cancer experiments is not magnetic, a magnetic field cannot push or control it. Magnetic responsiveness in bacteria is generally a very uncommon phenomena. One of the rare genera of bacteria with this characteristic is Magnetospirillum.
Schürle consequently desires to magnetically modify E. coli germs. This may eventually enable the use of a magnetic field to regulate therapeutically important medicinal microbes that don’t naturally exhibit magnetism.
