Scientists at the University of Texas Southwestern Medical Center have succeeded in delivering tumor suppressing therapies to cancer-affected livers with the help of nanoparticles, without inducing further liver damage or harming neighboring tissues. The findings were published in the journal Proceedings of the National Academy of Sciences (PNAS) in a study titled “Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model.”
Late stage liver cancer treatment is challenging to treat. Drugs that show good results when tested in healthy individuals may be toxic for patients with liver cancer – a condition leading to cirrhosis of the liver. Liver cancer is a leading cause of cancer death with a five-year survival rate of only 17 percent, according to the Centers for Disease Control and Prevention (CDC). The rates of liver cancer are increasing in the U.S., with higher rates seen among Asian people, and Hispanic and African-American males.
“Early-stage disease can be cured with surgery, but there are few options for cirrhotic patients with advanced liver cancers,” Zhu said in a UT Southwestern news release.
The research centers around microRNAs (miRNAs) – short nucleic acids that can act as natural tumor suppressors. But it’s not easy to deliver these miRNAs into cells because they are large and negatively charged.
The team at UT Southwestern synthesized more than 1,500 different kinds of nanoparticles, screening them for function as delivery systems in livers of mice with a highly aggressive form of liver cancer. They then identified nanoparticles, called dendrimers, that allowed the delivery of the miRNA to the liver cells without inferring further toxicity. The team observed that the miRNA delivered by the nanoparticles inhibited tumor growth and considerably extended survival of the mice. It is the first time anyone succeeded in producing carriers for miRNA cancer therapy that does not increase toxicity.
“We have synthesized highly effective dendrimer carriers that can deliver drugs to tumor cells without adverse side effects, even when the cancerous liver is consumed by the disease,” Siegwart said. “We found that efficacy required a combination of a small RNA drug that can suppress cancer growth and the carrier, thereby solving a critical issue in treating aggressive liver cancer and providing a guide for future drug development.”