Lung cancer, especially when diagnosed at stage 3 or 4, is notoriously difficult to treat. Only a fraction of patients respond to existing treatments, and the five-year survival rate is less than 18%. In an effort to improve those odds, a researcher at OU Health Stephenson Cancer Center is studying an innovative new approach to treatment — using tiny particles naturally produced by the body, loading them with chemotherapy and an imaging agent, then giving them directions to the cancerous cells.
Rajagopal Ramesh, Ph.D., recently earned a $2.8 million grant from the National Cancer Institute to conduct the promising study, one of only a few such projects funded in the United States. He is focusing on exosomes — nanometer-sized particles produced in the billions by the body’s cells. Exosomes are attractive as a drug delivery vehicle because of their nanoparticle size, which allows them to pass through tiny blood vessels to reach areas that conventional drugs cannot. And because exosomes are naturally produced, they are likely less toxic than particles that are synthesized using chemicals.
For this study, Ramesh’s use of exosomes is three-fold. First, he loads the exosomes with chemotherapy drugs. Then he adds iron oxide particles, the same agent that is used in MRIs to capture an image inside the body. Finally, he coats the entire exosome with a tumor-targeted peptide that essentially provides directions so that the exosomes travel to the cancerous cells instead of normal cells.
“Our preliminary data show that more than 90% of the exosome specifically goes to the tumor cells instead of harming normal cells with chemotherapy and causing side effects,” Ramesh said. “Once it reaches the tumor, we can monitor the killing of cancer cells in real time because of the imaging agent we loaded into the exosome. After treatment, we can again image the reduction of cancer cells. That’s why we call it a targeted multi-functional exosome.”
Lung cancer often metastasizes to the brain, liver and bone, which makes it especially difficult to treat with conventional therapies. Because exosomes are only 30 to 160 nanometers wide (for comparison, a human hair is approximately 100,000 nanometers wide), Ramesh hypothesizes that they will be able to reach those different areas efficiently and deliver the chemotherapy.
Decades ago, researchers considered exosomes “cellular garbage,” but over the past 10 to 15 years, the scientific community has reconsidered their role, Ramesh said. Both normal cells and cancer cells produce exosomes. Cancer cells produce a higher number of exosomes, and they seem to carry a message to normal cells telling them to transform into cancer cells, he said. Researchers then began thinking about using exosomes from normal cells to deliver drugs to cancer cells.
If Ramesh’s laboratory study is successful, his next steps would be to scale up the production of exosomes to be tested in humans as drug delivery vehicles. The concept is encouraging for its potential to “outsmart” clever tumor cells.
“The challenge we have with cancer, in particular lung cancer, is that tumor cells have the ability to modify themselves in a way that the drugs cannot recognize them anymore. It’s like a cop constantly chasing a thief,” he said. “That’s why we are trying this new option to see if we can prove the concept.”
Research reported in this news release is supported by the National Cancer Institute, a component of the National Institutes of Health, under the award number 1R01CA254192-01A1. The project also has been supported by the Presbyterian Health Foundation in Oklahoma City and the Jim and Christy Everest Endowed Chair in Cancer Developmental Therapeutics Research, which Ramesh holds.
