▎ WuXi AppTec content team editor
In cancer treatment, conventional chemotherapy has helped many patients to prolong survival, but chemotherapy still has no small side effects. Because chemical drugs will indiscriminately attack cells that proliferate rapidly, cells like healthy hair follicles and gastric wall cells will be damaged in a large area, and patients will lose their hair and nausea.
In order to snipe cancer cells more accurately and protect the survival of healthy cells, scientists are also seeking better alternative treatments, and a class of potential assistants is the microbes that we usually feel are also dangerous. Researchers at the California Institute of Technology recently designed an engineered, sound-controllable class of bacteria that serve as tools to precisely kill cancer cells. When bacteria are injected into mice, they can penetrate into the inside of the tumor, at which point researchers can trigger the installation of switches in the bacteria to release anti-cancer drugs.
According to the Nature Communications paper, the study used an E. coli called Nissle 1917, whose safety has first been verified and approved for use in human medical pathways. After entering the bloodstream, these bacteria will move throughout the body, of course, our immune system will not be idle, will remove most of the bacteria, but there is only one place they can not do anything, that is, the tumor area. Because immunosuppression often occurs in the tumor microenvironment, bacteria that migrate here also survive.
With the premise of specifically settling tumors, the research team decided to engineer the bacteria to insert new genes to allow it to carry the characteristics we needed. The first introduced gene is used to produce nanoinves that are able to suppress proteins that tumors resist the immune system, breaking down the immunosuppressive tumor microenvironment. The other gene is similar to a thermal induction switch, which activates the nano-antibody gene only when the temperature reaches a certain limit, which is equivalent to controlling the expression of the nano-antibody.
Image credit: 123RF
In the experiment, the activation condition of this temperature switch is 42-43 ° C, which means that the nanoantibodies will not be released at normal body temperature, and the researchers need to create a warming situation through external introduction conditions. Of course, some tumors are deep in the body, and bacteria cannot reach them by heating the body surface.
Here, the researchers specifically used ultrasonic focusing technology, which can use ultrasonic waves as energy sources to emit most sound waves deep in the body and focus, controlling the temperature of the local area through the conversion of sound waves and thermal energy. The tissue around the focal point is not affected, so it only exposes the tumor to a special temperature environment.
▲The use of ultrasound through specific areas can activate the release of anti-cancer nano-antibodies by engineered bacteria in mice (Image source: Reference[1])
To test whether the engineered bacteria would work as expected, they selected a batch of tumor mice, and after the tumors had grown to a certain size, the mice underwent bacterial injections. The ultrasound technique used in the study can increase the temperature of the tumor area from 37 °C to 43 °C for 5 minutes. After the experiment, the researchers took samples and analyzed the tumor samples.
Compared with the control group, ultrasound technology with engineered bacteria can significantly reduce the tumor volume, and the engineered bacteria in the tumor can still survive for more than two weeks after being activated. One of the 6 treated tumors disappeared completely after treatment. In addition, these engineered bacteria only gather in the tumor area, and the number of engineered bacteria in the liver and spleen samples of mice is very low, and the only side effect is that the skin may have some burns.
"These results are very optimistic, and it shows that we can provide targeted therapy for tumors at the right time," said lead author Mikhail Shapiro, Ph.D., who in the future they considered improvements by trying to visualize engineered bacteria before using ultrasound, ensuring that activation was effective so that tumors could be treated more precisely.
Resources:
[2] Researchers develop sound-controlled bacteria to fight cancer. Retrieved Mar 29th, 2022 from https://medicalxpress.com/news/2022-03-sound-controlled-bacteria-cancer.html
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