Researchers in China have developed a new three-pronged method to fight liver cancer that shows promise in tests in mice. The technique combines drugs and CRISPR-Cas9 gene editing into lipid nanoparticles, then activates them with ultrasound.
One emerging treatment against cancer is known as sonodynamic therapy (SDT), which involves delivering drugs to the tumor and then activating them with ultrasound pulses. That produces reactive oxygen species (ROS) that can induce oxidative stress on the cancer cells to kill them. Unfortunately, cancer can counter this attack with antioxidant enzymes, reducing the method’s efficiency.
So for the new study, the researchers investigated a way to remove that defense system. The team suspected that they could use CRISPR to switch off a gene called NFE2L2, which cancer cells use to set off their antioxidant defenses. The team packaged both the CRISPR machinery and the ROS-producing drugs into lipid nanoparticles, which could be activated with ultrasound pulses.
First, the team tested the technique in a dish on cells from a type of liver cancer called hepatocellular carcinoma. The cells took up the nanoparticles, and when ultrasound was applied ROS were formed, which broke open the cells’ lysosomes. That in turn let CRISPR enter the cells’ nuclei, where it got to work knocking out expression of NFE2L2. As such, more ROS were produced, damaging and killing significantly more of the cancer cells compared to the same technique without the gene editing.
In follow-up experiments, the team tested the technique in mice with implanted human hepatocellular carcinoma. While SDT alone did reduce the number of tumors compared to untreated mice, the animals that received both the nanoparticles and ultrasound together saw all of their tumors shrink after 15 days.
The team says that the technique should have fewer side effects than other treatments, because ROS and CRISPR are only released into cells in the area where the ultrasound pulses are directed. Ultrasound can also penetrate deeper into tissue than a related technique called photodynamic therapy, which is triggered by infrared light instead.
Of course, the scientists still need to cross the chasm between animal tests and human trials, with no guarantee that the technique will be applicable to us. But it’s an interesting new tool to investigate.
The research was published in the journal ACS Central Science.
Source: American Chemical Society