Sonodynamic therapy uses ultrasound in combination with drugs to release harmful reactive oxygen types (ROS) at the website of a tumor. Now, scientists reporting in ACS Central Science have breached these defenses with CRISPR/Cas9 gene modifying, allowing sonodynamic treatment to efficiently diminish growths in a mouse design of liver cancer.
Ultrasound treatment caused ROS formation, which burst lysosomes and allowed the CRISPR/Cas9 system to knock and go into the nucleus down NFE2L2 gene expression. Mice treated with sonodynamic therapy alone had fewer tumors than untreated mice, but the addition of the CRISPR/Cas9 system substantially enhanced the treatments effectiveness.
Next, the group injected the nanoparticle treatment into mice with implanted human hepatocellular carcinoma tumors. After 15 days of the combined nanoparticle and ultrasound treatment, all of the tumors in the mice disappeared and didnt come back. Mice treated with sonodynamic therapy alone had fewer tumors than untreated mice, however the addition of the CRISPR/Cas9 system significantly enhanced the treatments efficiency. Since gene modifying takes place only in growth tissues under ultrasound irradiation, it will not cause gene anomalies in healthy tissues, the scientists state.
Reference: “Ultrasound-Controlled CRISPR/Cas9 System Augments Sonodynamic Therapy of Hepatocellular Carcinoma” 8 December 2021, ACS Central Science.DOI: 10.1021/ acscentsci.1 c01143.
The authors acknowledge funding from the National Natural Science Foundation of China and Shanghai Municipal Health Commission.
Ultrasound irradiation of a tumor causes a lipid nanoparticle (drawing shown above) to launch hazardous ROS and a CRISPR/Cas9 gene-editing system. Credit: Adapted from ACS Central Science 2021, DOI: 10.1021/ acscentsci.1 c01143.
Sonodynamic therapy utilizes ultrasound in mix with drugs to release damaging reactive oxygen types (ROS) at the site of a growth. Nevertheless, the treatment isnt very reliable due to the fact that cancer cells can trigger antioxidant defense systems to combat it. Now, scientists reporting in ACS Central Science have breached these defenses with CRISPR/Cas9 gene editing, permitting sonodynamic therapy to efficiently diminish growths in a mouse design of liver cancer.
Because ultrasound can penetrate deep within tissues, sonodynamic treatment could be an effective, non-invasive way to deal with hepatocellular carcinoma. Presently, cancer cells can quickly overcome the treatment by activating a gene called nuclear factor erythroid 2-related aspect 2 (NFE2L2), which deploys the cells detoxification and antioxidant enzyme defenses.
As a primary step, the scientists encapsulated the CRISPR/Cas9 system and an ROS precursor molecule in lipid nanoparticles. They dealt with hepatocellular cancer cells in a petri dish with the nanoparticles. The lipid nanoparticles were used up by the cells lysosomes. Ultrasound treatment caused ROS development, which ruptured lysosomes and allowed the CRISPR/Cas9 system to knock and enter the nucleus down NFE2L2 gene expression. The ROS also damaged other cellular elements. As an outcome, substantially more cancer cells died from the sonodynamic therapy than without NFE2L2 gene editing.
