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It goes without saying that magnets have uses beyond simply pinning wedding RSVPs to your refrigerator. In medicine, magnetism is a crucial component of magnetic resonance imaging (MRI), an invaluable diagnostic tool for clinicians. An MRI subjects the human body to an enormous magnetic field ‒ perhaps a thousand-fold more than a common fridge magnet ‒ to image our internal organs without cutting through our skin. Though this may sound frightening, MRIs are considered one of the safest tools available, especially for diagnosing and staging cancers. However, the potential of magnets in the direct treatment of cancer has not been fully recognized.
A common and dreaded approach to cancer treatment is chemotherapy, wherein a toxic compound is administered to kill cancer cells before major organ damage occurs. Many chemotherapies are toxic because they often disrupt the same life-sustaining processes required for all cells, not just cancer cells. Thus, an active thread of cancer therapy research has focused on targeting drugs specifically to the tumor while avoiding normal organs.
One idea proposed a few decades ago was using magnets to concentrate a “magnetic” drug into the region of a tumor. In this way, a lower amount of the toxic drug is required. Also, the systemic spread of the drug ‒ that is, its ability to reach other healthy regions of the body ‒ is limited. Unfortunately, many early attempts at reifying this approach have not come to fruition.
In a recent paper, a group of researchers at ETH Zurich introduced a novel method by which magnets can direct drug-carrying bacteria toward tumor sites. They show promising evidence that a rotating magnetic field (RMF) can effectively coax magnetic bacteria across cell barriers and into tumors.
As the name suggests, RMFs generate a force on magnetic objects that promotes rotative movement. This is the same phenomenon employed in electric cars to make wheels spin, without the need for gasoline-driven pistons. In contrast, a directional magnetic field (DMF) describes the type of attraction seen with fridge magnets. Theoretically, DMF can also be used to simply pull bacteria toward a tumor. However, in practice, this navigational approach would be too crude and would require a large and impractical amount of energy.
Using RMF, the researchers first demonstrated that magnetic bacteria can cross a cell barrier better. The bacterial strain they focused on is Magnetospirillum magneticum (M magneticumt). M magneticum are naturally magnetic because they synthesize magnetic particles known as magnetite. Importantly, these bacteria can be linked to liposomes, which are membranous structures that can be packaged with anti-cancer drugs. For example, in a transwell system, where two liquid compartments are separated by a barrier of cells, RMF was better able to push bacteria across from one compartment to the other compared to DMF or when no magnetic field was applied. This is important because for circulating bacteria to infiltrate a tumor, they need to pass through an endothelial barrier or the wall of cells that fortify blood vessels.
To understand why RMF was better able to push M magneticum across a cell barrier, the researchers relied on computer simulations. They modeled the endothelial barrier as a wall with doors that randomly open and close. The effect of RMF was modeled as ovoid bacterial particles that constantly rotated, whereas DMF was modeled as ovoid particles that were simply pulled toward the wall. Using this simulation, the researchers realized that rotating particles (the RMF condition) could move along and explore the wall. Therefore, they had higher chances of encountering and trespassing an open door. Motionless particles emulating the DMF condition remained attached to the wall.
The ability to cross the endothelial barrier is helpful for a good cancer-smiting bacteria. But, it is not enough. These microscopic Trojan horses need to also dive deep into the dark of the tumor mass itself. As such, the scientists created a 3D ball of tightly-packed cancer cells known as spheroids to find out if their M magneticum can penetrate into the tumor body. When these spheroids were incubated with M magneticum under RMF, the researchers found that these bacteria were better able to enter the spheroids than when no magnetic field was applied. This finding strengthens the utility of using RMF to not only help bacteria exit the bloodstream, but also penetrate deep into the tumor.
Whether this RMF approach was effective in a living body, not just a petri dish, remained. To address this, the researchers injected bacteria into the bloodstream of tumor-carrying mice and subjected them to RMF. Compared to mice given DMF or no magnetic field, RMF treatment resulted in higher levels of bacteria infiltrating the tumors . Excitingly, they also found that most other organs were not infiltrated with bacteria. This strongly supports using the RMF method to specifically target drug-carrying bacteria toward tumors while avoiding normal organs. Collectively, this will minimize the terrible side-effects of most chemotherapeutics.
Unfortunately, the scientists did not report any data demonstrating that M magneticum loaded with anti-cancer drugs and homed with RMF can better eliminate tumors in mice. Furthermore, a requisite of using this approach in a clinical setting is prior knowledge of the tumor location, in order to magnetically inform the bacteria of where to go. Thus, this approach may not be efficacious in cases of metastatic cancer, where a tumor sets up shop in multiple locations of the body, which can be difficult to track.
Regardless, the findings presented represent an impressive leap in this field of “medical microrobotics.” Using drug-carrying magnetic bacteria exploits the innate properties of magnetic responsiveness and the natural ability to migrate within normal and cancerous tissues. As such, this improves their ability to be guided specifically toward and into tumors, where they can release anti-cancer toxins. As a bonus, the presence of bacteria in a tumor can prompt an anti-cancer immune response, often an effective mechanism of eliminating cancer cells. Overall, these findings lend hope for a future where magnets become an essential tool for fighting cancer.
Edited by Aishat Motolani
Gwisai, T., Mirkhani, N., Christiansen, M.G., Nguyen, T.T., Ling, V., Schuerle, S., 2022. Magnetic torque–driven living microrobots for increased tumor infiltration. Science Robotics 7, eabo0665. https://doi.org/10.1126/scirobotics.abo0665
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