New experimental therapies for cancer include CRISPR gene editing, drugs and ultrasound.
Researchers in China have developed a new three-pronged method to fight liver cancer, which has already worked in mice. The approach combines drugs and editing of the CRISPR-Cas9 gene into lipid nanoparticles, and then activates them using ultrasound.
One of the newer cancer treatments is called sonodynamic therapy (SDT), during which the drug is delivered to the tumor and then activated by ultrasound pulses. This leads to the formation of reactive oxygen species (ROS), which can cause oxidative stress on cancer cells to kill them. Unfortunately, cancer can counter this attack with antioxidant enzymes, making the method less effective.
So in a new study, the authors explored how to bypass this defense system. They theorized that CRISPR could be used to disable the NFE2L2 gene, which cancer cells use to activate their antioxidant defenses.
The researchers put the CRISPR tool and ROS-producing drugs in lipid nanoparticles that can be activated by ultrasonic pulses.
The technique was tested first on liver cancer cells. The cells absorbed the nanoparticles, and when using ultrasound, ROS were formed, which ruptured the lysosomes of the cells. This, in turn, allowed CRISPR to enter the cell nuclei, where it began to work by suppressing the expression of NFE2L2. As a result, more ROS were produced, which damage and kill cancer cells, compared to similar methods that do not use gene editing.
In subsequent experiments, the team tested the method in mice with implanted hepatocellular carcinoma. In animals that received both nanoparticles and ultrasound together, all tumors shrank significantly after 15 days.