Fight tumors with magnetic bacteria

Scientists around the world are studying how cancer drugs can most effectively reach targeted tumors
.
One possibility is to use engineered bacteria as a "ferry" to transport drugs through the bloodstream to tumors
.
Researchers at ETH Zurich have now succeeded in controlling certain bacteria, allowing them to effectively cross the walls of blood vessels and penetrate into tumor tissue
.

Under the leadership of Prof.
Simone Schürle in response to the biomedical system, ETH Zurich researchers have selected a bacterium that is naturally magnetic
due to its iron oxide particles 。 The bacteria of these genera Magnetospirillum react to magnetic fields and can be controlled by extracorporeal magnets; For more information, see an earlier article on ETH News[https://ethz.
ch/en/news-and-events/eth-news/news/2020/12/magnetic-bacteria-as-micropumps.
html].

Take advantage of temporary gaps

In cell culture and mice, Schürle and her team have now shown that applying a rotating magnetic field to tumors improves the bacteria's ability to
move through blood vessel walls near where the cancer grows.
At the walls of blood vessels, a rotating magnetic field pushes the bacteria forward
in a circular motion.

To better understand the working mechanism across the vessel wall, it is necessary to make a detailed observation: the vessel wall consists of a layer of cells, which acts as a barrier between the bloodstream and the tumor tissue, which is penetrated
by many small blood vessels.
The narrow space between these cells allows certain molecules to pass through the walls
of blood vessels.
The size of these intercellular spaces is regulated by the cells of the blood vessel wall, and they can be temporarily wide enough to even allow bacteria to pass through the blood vessel wall
.

Strong propulsion and high probability

With the help of experiments and computer simulations, ETH Zurich researchers were able to demonstrate that using rotating magnetic fields to push bacteria is effective for three
reasons.
First, the propulsion force through the rotating magnetic field is ten times
the propulsion force through the static magnetic field.
The latter simply sets the direction, and the bacteria must move
on their own.

The second and most critical reason is that bacteria are constantly moving along the walls of blood vessels driven by a rotating magnetic field
.
This makes it more likely that they will encounter short-open gaps between the cells of the vessel wall, where the movement of bacteria is less explored
than in other propulsion types.
Third, unlike other methods, bacteria do not need to be tracked
by imaging.
Once the magnetic field is localized on the tumor, it does not need to be readjusted
.

"Cargo" accumulates in tumor tissue

"We also take advantage of the natural and autonomous movement of bacteria," explains Schürle
.
"Once bacteria cross the blood vessel wall into the tumor, they can independently migrate
deep inside the tumor.
" For this reason, the scientists used an external magnetic field to prostace for only an hour — enough for bacteria to efficiently cross the walls of blood vessels to reach the tumor
.

This bacterium may carry anti-cancer drugs
in the future.
In their cell culture study, ETH Zurich researchers simulated this application
by attaching liposomes (nanospheres of fat-like substances) to bacteria.
They labeled these liposomes with fluorescent dyes, which allowed them to prove in a dish that bacteria did indeed transport their "cargo" into cancerous tissue, where they accumulated
.
In future medical applications, liposomes will be filled
with drugs.

Bacterial cancer treatment

Using bacteria as a transporter for drugs is one of
two ways bacteria can help fight cancer.
Another approach, which is more than a hundred years old and is currently being revived: exploiting the natural propensity of certain species of bacteria to destroy tumor cells
.
This can involve several mechanisms
.
In any case, bacteria are known to stimulate certain cells of the immune system and then eliminate tumors
.

Multiple research projects are currently investigating E.
coli bacteria on tumors
.
Today, it is possible to modify bacteria using synthetic biology to optimize their therapeutic outcomes, reduce side effects, and make them safer
.

Make non-magnetic bacteria magnetic

However, to use the inherent properties of bacteria in cancer treatment, the question of how effectively these bacteria reach tumors remains
.
While it is possible to inject bacteria directly into tumors near the surface of the body, this is not possible
for tumors deep in the body.
This is where Professor Schürle's microrobot control comes in
.
"We believe we can use our engineering approach to improve the efficacy
of bacterial cancer treatments," she said.

E.
coli used in cancer research is not magnetic and therefore cannot be pushed and controlled
by magnetic fields.
In general, the magnetic reactivity of bacteria is a very rare phenomenon
.
Magnetospirillum is one
of the few bacterial genera with this property.

Schürle therefore wanted to make E.
coli bacteria also magnetic
.
This could one day make it possible to use magnetic fields to control clinically used therapeutic bacteria that don't have natural magnetism
.

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