Focused ultrasound turns chemo from shotgun blast to sniper shot
When fighting cancer, chemotherapy is still a bit of a blunt instrument. By combining it with soundwaves, however, researchers have found a way to turn it into more of a scalpel than a club, sparing damage to nearby tissue and the body as a whole.
Even though the number of ways doctors can fight cancer is rapidly increasing, traditional chemotherapy is still widely used to combat tumors. In fact, according to a study in The Lancet Oncology, it is predicted that the number of people needing the treatment is set to increase by 53% between 2018 and 2040. But many of the well-known issues with chemotherapy still exist: it can cause hair loss, nausea, weight loss, anemia, peripheral neuropathy, and more. Plus, because chemo drugs treat the whole body, they can cause damage to cells outside of the intended tumor targets.
Attempting to make chemotherapy a more targeted solution, researchers in 2020 combined cancer-fighting chemicals with bursts of laser light to activate them at tumor sites. While that treatment shows promise, its efficacy is limited to a few millimeters below the skin, which is the maximum depth a laser beam can penetrate in order to activate the chemicals.
Seeking to harness the power of the targeted activation of chemotherapeutic drugs but increase the depths at which they can function, scientists at the City University of Hong Kong (CityU) turned to the idea of using soundwaves.
Working with cancer cell cultures in their lab, the researchers created a small-molecule platinum-based prodrug called cyaninplatin, which gathered at the tumor sites. Prodrugs are compounds that are inert until they are activated inside the body. They then beamed the cyaninplatin with highly-targeted ultrasound waves, which converted it to carboplatin, a common chemotherapy drug. This induced tumor death by damaging the mitochondria inside the cancer cells.
The method was able to reduce cancer cell viability by 51% when tissue coverage was 1 cm thick (about 0.4 in) and 33% with tissue coverage at a thickness of 2 cm.
Further testing in mice showed that the method was able to completely eliminate two tumors after six days of treatment and dramatically inhibit the growth of additional tumors.
“Our well-designed functional ultrasound enables the sono-sensitized chemotherapy to be a precise tumor-specific treatment with good penetration performance,” said study co-author Zhu Guangyu from CityU's Department of Chemistry. “More importantly, our system allows the ultrasound to focus on a specific area within 8 mm, and hence highly focuses the ultrasound energy on a tiny area to activate sono-responsive prodrugs, providing an efficient approach with minimal side effects.”
In addition, because cyaninplatin fluoresces, the researchers found that their method can also be used as an imaging system that can allow for 3D mapping of tumors, precise guidance of the drug particles, and real-time monitoring of the drug's accumulation in tumors.
The research has been published in the journal Science Advances.
Source: City University of Hong Kong