Jefferson researchers discover that nanoparticle shows promise in reducing radiation side effects

(PHILADELPHIA) Using transparent zebrafish embryos, researchers at Jefferson Medical College in Philadelphia have shown that a microscopic nanoparticle can help fend off damage to normal tissue from radiation. The nanoparticle, a soccer ball-shaped, hollow, carbon-based structure known as a fullerene, acts like an "oxygen sink," binding to dangerous oxygen radicals produced by radiation.

The scientists, led by Adam P. Dicker, M.D., Ph.D., and Ulrich Rodeck, M.D., see fullerenes as a potentially "new class of radioprotective agents." Dr. Dicker, recently appointed Vice-Chair for Translational Research of the Radiation Therapy Oncology Group, is associate professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University and at the Kimmel Cancer Center at Jefferson. Dr. Rodeck is professor of dermatology at Jefferson Medical College. They will present their team's results April 5, 2006 at the annual meeting of American Association for Cancer Research in Washington, D.C.

While chemotherapy and radiotherapy are the standard treatments for cancer, they take their respective toll on the body. Radiation can damage epithelial cells and lead to permanent hair loss, among other effects, and certain types of systemic chemotherapy can produce hearing loss and damage to a number of organs, including the heart and kidneys. Some other side effects include esophagitis, diarrhea, and mouth and intestinal ulcers.

To date, only one drug, Amifostine, has been approved by the federal Food and Drug Administration, to help protect normal tissue from the side effects of chemotherapy and radiation. Researchers would like to develop new and improved agents.

Dr. Dicker, director of the Division of Experimental Radiation Oncology at Jefferson Medical College, and his group were exploring the molecular mechanisms responsible for cellular damage from radiation. They collaborated with a Houston-based drug company, C Sixty, and studied its radiation-protective agent, CD60_DF1.

To test how well it worked, they turned to tiny zebrafish embryos, which are transparent for the first month of life and allow scientists to observe closely organ damage produced by cancer treatments. Zebrafish have most of their organs formed by the third day after fertilization.

They gave the embryos different doses of ionizing radiation as well as treatment by either Amifostine, which acted as a control agent, or CD60_DF1. First, they found that CD60_DF1 had almost no toxicity. Then, they saw that CD60_DF1 given before and even immediately after--up to 30 minutes--exposure to X-rays reduced organ damage by one-half to two-thirds, which was as good as the level of protection given by Amifostine.

"We also showed that the fullerene provided organ-specific protection," Dr. Dicker notes. "It protected the kidney from radiation-induced damage, for example, as well as certain parts of the nervous system."

He explains that one way that radiation frequently damages cells and tissues is by producing "reactive oxygen species"--oxygen radicals, peroxides and hydroxyls. The scientists showed that zebrafish embryos exposed to ionizing radiation had more than 50 percent reduction in the production of reactive oxygen species compared to untreated embryos.

Dr. Dicker says that the company has technology enabling certain molecules to be attached to the nanoparticles, which will allow for targeting to specific tissue and organs, further enhancing use of the nanoparticles.

Dr. Dicker and his team plan follow-up studies using mouse models that will allow them to find out whether fullerene protects the entire animal from radiation, and how it works to protect specific organs. They also are interested in exploring its ability to prevent long-term side effects of radiation, such as fibrosis.

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The research was supported by the Commonwealth of Pennsylvania and a seed grant from the Radiation Therapy Oncology Group.


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