What is the most efficient way for cancer drugs to reach their target site in tumors? A study now shows that magnetic bacteria could help. Loaded with the active ingredient, the biohybrid microrobots can be guided to the tumor by an externally applied magnetic field, can penetrate it and release the chemotherapeutic agent there. Experiments in cell cultures and mice were promising.
Bacteria of the genus Magnetospirillum live in oxygen-poor waters and absorb dissolved iron from their environment. As a result, they become magnetic themselves and can orientate themselves using the earth's magnetic field. This property also makes them interesting for research. An earlier study has already shown that they can be moved and controlled with the help of magnetic fields. The bacteria also move to areas with their preferred low oxygen concentrations of their own accord. Such conditions prevail, among other things, inside many tumors.
living microrobots
A team led by Tinotenda Gwisai from ETH Zurich has now tested how the special properties of Magnetospirillum could be used for targeted tumor therapy. "Bacterial-based biohybrid microrobots are gaining recognition as promising remotely controllable vehicles for targeted cancer therapy," the authors write. "Magnetic fields in particular are considered a safe means of transmitting energy and controlling its movement."
The idea behind it: Instead of simply administering a chemotherapeutic agent into the bloodstream, from where it not only reaches the tumor but also many other regions of the body and causes damage there, the bacteria should transport the drug directly to the tumor and only release it there . This should make the therapy more effective and at the same time reduce side effects. The challenges here: On the one hand, the bacteria first have to get close to the tumor, on the other hand they have to penetrate the vessel wall there in order to get out of the blood vessel and into the tumor.
Signpost and drive in one
In cell cultures and in mice, Gwisai and her team have now investigated how an externally applied magnetic field can help. In one experiment, they injected mice with tumors with the bacteria into the tail vein and directed a rotating magnetic field at the tumor. After 24 hours, they examined how many bacteria had accumulated in the tumor. And indeed: most of the bacteria were actually in the tumor; only a few had accumulated in other organs.
With the help of further experiments and computer simulations, the researchers proved that the rotating magnetic field helps in several ways: First, it captures all bacteria that come within range of the magnetic field and steers them in the right direction. In addition, unlike a static magnetic field, it causes them to rotate around their own axis and keeps them constantly moving. This makes it easier for the bacteria to squeeze through temporary gaps in the wall of the blood vessels near the tumor and penetrate the tumor. The magnetic field not only sets the direction, but also provides the drive.
Bacterial Cancer Therapy
In addition to the magnetic field, the researchers are also relying on the bacteria's own tendency to move to low-oxygen areas. "We also use the natural and autonomous movement of bacteria," explains Gwisai's colleague Simone Schürle. "Once the bacteria have passed through the blood vessel wall and are in the tumour, they can autonomously penetrate deep into it." In cell cultures and three-dimensional tumor models, the researchers also demonstrated that the bacteria are actually able to transport cargo into the tumour transport. To do this, they attached nanobubbles made of fatty substances, so-called liposomes, that were filled with a fluorescent dye to the bacteria. As hoped, the dye accumulated inside the tumor tissue. A medicine could be transported in the same way.
In future studies, the research team now wants to clarify the extent to which other bacteria that are not naturally magnetic can also be used in cancer therapy. In addition, it could be possible to manipulate medically well-researched bacteria such as Escherichia coli in such a way that they also become magnetic. In addition, bacteria could possibly be used in the same way, which previous studies have already shown that they cause the immune system to attack cancer cells more intensively. "We think that with our engineering approach we can increase the effectiveness of bacterial cancer therapy," says Schürle.
Source: ETH Zurich, specialist article: Tinotenda Gwisai et al., Science Robotics, doi: 10.1126/scirobotics.abo0665