Cells in the human body release nano-sized bubbles that transfer genetic material such as DNA and RNA to other cells. These bubbles could carry drugs and genes that target and kill cancer cells, according to researchers from East Lansing’s Michigan State University and California’s Stanford University.
The study focused on breast cancer cells in mice and was published in Molecular Cancer Therapeutics.
“What we’ve done is improve a therapeutic approach to delivering enzyme-producing genes that can convert certain drugs into toxic agents and target tumors,” says Masamitsu Kanada, lead author and assistant professor of pharmacology and toxicology in MSU’s Institute for Quantitative Health Science and Engineering.
These drugs, which are called prodrugs, start out as inactive compounds and are metabolized in the body, activating them. Once they’re activated, they can fight everything from cancer to headaches. Aspirin is an example of a common prodrug.
Researchers used extracellular vesicles to deliver the enzyme-producing genes that could activate a prodrug therapy of ganciclovir and CB1954 in breast cancer cells. Minicircle DNA and regular plasmid – two gene vectors that act as additional delivery mechanisms for DNA – were loaded into the vesicles to see which was better at transporting treatment. This is known as gene-directed enzyme, prodrug therapy.
They found that the minicircle DNA was 14 more times more effective at delivery and even more successful at killing cancerous tumors.
“Interestingly, the plasmid delivery method didn’t show any tumor cell killing,” says Kanada. “Yet the minicircle DNA-based therapy killed more than half of the breast cancer cells in the mice.”
Kanada says this new approach could become a more effective cancer treatment than chemotherapy.
“Conventional chemotherapy isn’t able to differentiate between tumors and normal tissue, so it attacks it all,” Kanada says. “This non-specificity can cause severe side effects and insufficient drug concentration in tumors.”
With extracellular vesicles, treatment can be targeted because of its compatibility with the human body. The delivery could minimize the risk of unwanted immune responses that can come with other gene therapies, making it a better option for such treatments.
A phase-one clinical trial, separate from Kanada’s work, is set to start soon in the U.S. and will use extracellular vesicles and a type of therapeutic RNA molecule for the treatment of metastatic pancreatic cancer.
While the trial moves forward, Kanada and his team will continue to further engineer and test the vesicles, improving their effectiveness and safety.
The study was funded in part by the National Institutes of Health.