SCIENTIFIC EDUCATIONAL CENTER science idea

Chinese researchers have developed a new three-component method of fighting liver cancer, which has shown promise in tests on mice. This method combines drugs and editing of the CRISPR-Cas9 gene into lipid nanoparticles, and then activates them with ultrasound.

One of the new cancer treatment methods is known as sonodynamic therapy (SDT), which involves the delivery of drugs to the tumor and their subsequent activation by ultrasound pulses. This produces reactive oxygen species (ROS), which can cause oxidative stress in cancer cells and kill them. Unfortunately, cancer can resist this attack with the help of antioxidant enzymes, reducing the effectiveness of the method.

In a new paper, researchers have studied a way to eliminate this protective system. The team suspected they could use CRISPR to disable a gene called NFE2L2, which cancer cells use to activate their antioxidant defenses. The scientists packed both the CRISPR instrument and the ROS-producing drugs into lipid nanoparticles that could be activated by ultrasound pulses.

First, they tested this technique in vitro on liver cancer cells called hepatocellular carcinoma. The cells absorbed the nanoparticles, and when ultrasound was used, ROS were formed, which destroyed the lysosomes of the cells. This, in turn, allowed CRISPR to penetrate into the cell nuclei, where it began to work, suppressing the expression of NFE2L2.

Thus, more ROS were produced, damaging and killing significantly more cancer cells compared to the same method without gene editing.

In subsequent experiments, the scientists tested the technique on mice with implanted human hepatocellular carcinoma. While only SDT actually reduced the number of tumors compared to other mice without therapy, in animals treated with nanoparticles and ultrasound at the same time, all their tumors decreased after 15 days.

Scientists say that this method should have fewer side effects than other treatments, because ROS and CRISPR only enter cells in the area where the ultrasound pulses are directed. Ultrasound can also penetrate deeper into the tissue than a related technique called photodynamic therapy, which is instead triggered by infrared light.

Of course, scientists still have to overcome the distance between animal testing and human testing, without a guarantee that the method will be applicable to us. But this is an interesting new tool for research.

An article about the study was published in the journal ACS Central Science.

ab-news.ru (Alla Konaka)