Tech & Innovation in Healthcare

Cancer treatments usually involve chemotherapy or immunotherapy infusions that can cause side effects in the patient. Researchers in Switzerland have discovered magnetic bacteria that can be guided into tumors to deliver precision cancer treatment.

Mind the Cell Wall Gaps

The biological barrier of the blood vessels is made of endothelial cells. In tumors, these cells frequently open and close, and this stochastic open/close process creates temporary gaps in the cells. The biohybrid bacteria-based microrobots can then squeeze through the gaps to attack the tumors. However, the bacteria need to be close to the blood vessel wall’s surface to exploit the cell gaps.

“We drive the bacteria into tumors by applying rotating magnetic fields which imparts a torque on their motion and makes them roll along surfaces and helps them find these cell gaps and then push themselves into tumors,” says Simone Schuerle, PhD, assistant professor (tenure track), Institute of Translational Medicine, Head of the Responsive Biomedical Systems Laboratory, ETH Zurich, Switzerland. By keeping the bacteria near the blood vessel wall’s surface, the bacteria can explore the surface to increase the chance of finding the cell gap.

Drive the Bacteria Into the Tumor

Dr. Schuerle and the research team have compared their rotating magnetic field approach to other methods, like directing the magnetic bacteria toward the tumor with magnetic fields pointing the bacteria to the target. However, researchers found several drawbacks to the other methods, including:

• Relying solely on the bacterial motor’s power to move the bacteria forward
• Bacteria are unable to locate the cell gaps
• Approach is ill suited for intravenous (IV) applications

Whereas a rotating field allowed the researchers to apply greater force to the bacteria. “The torque we exert is an order of magnitude higher than the propulsive force the bacteria’s molecular motor can generate, and we could increase the external torque further if needed by increasing the external magnetic field strength,” Dr. Schuerle says.

The research team used a set of electromagnets to generate 3D homogenous rotating fields from a device that was approximately the size of a shoebox. This device was integrated into a high-resolution confocal microscope which allowed the researchers to perform initial magnetic actuation studies with mini tumor models in a petri dish, while observing the bacteria movement in real-time. Researchers also used the same device for follow-up studies with mice. Although for human scale studies, other system designs are needed, which the team is already planning. Alternatively, by attaching a permanent magnet to a robotic arm that rotates, researchers can also create a rotating magnetic field.

Dr. Schuerle explained three reasons why the rotational magnetic field works well with the hybrid bacteria:

1) Efficiency: Researchers found that the rotating magnetic field outperformed the static magnetic field significantly.

2) Movement: The rotating magnetic field rolls the bacteria along vessel walls, which gives the bacteria a better chance of finding cell gaps and infiltrating the tumor. “We ‘simply’ need to know where the tumor is, which we would infer beforehand via a detailed positron emission tomography (PET) scan, then focus the rotating field into that region,” Dr. Schuerle adds.

3) No imaging needed: With the detailed PET scans providing the tumor’s general location, researchers can then focus the rotating magnetic field into that area without the need for continuous image guidance.

In an April 2023 preprint, Dr. Schuerle and her team presented a new design including simulation on the effect of focused sweeping rotating magnetic fields. The researchers showed that by combining gating fields and rotating magnetic fields, they can provide focused torque density to dispersed microrobots.

“We aim to build a human-scale system that could set focus in different body regions to potentially hit different metastatic sites one by one,” Dr. Schuerle added.

Session length: If this treatment were to become a practical therapeutic option, each session may last around 60 minutes upon injection. This duration was used in initial animal studies and would need to be tested whether the time is sufficient for the bacteria to pass through the cell wall and embed themselves in the tumor.

The rotating magnetic field allows the scientists to override the bacteria’s natural movements to guide the bacteria toward the tumor, but the bacteria’s natural tendencies take over once it reaches the malignancy.

“We still leverage the bacteria’s innate taxis and that they, once engrafted in tumor tissues, would try to reach hypoxic regions deeper within it, since they are anaerobic and prefer the low oxygen environment,” Dr. Schuerle explains.

When Could Physicians Start Administering Magnetic Bacteria?

While the equipment to create the magnetic field may see real-world use soon, physicians deploying magnetic bacteria to treat tumors will require more time for research. “The magnetic systems could be in use probably earlier as they could be also applied to other applications, but the magnetic bacteria will have a longer path towards translation,” Dr. Schuerle says.

Dr. Schuerle added that while therapeutic use in human patients may still be 10 to 15 years away, she remains very optimistic about the research.