Nanoparticle-Based Treatment in Melanoma

Penn State College of Medicine researchers have discovered a new class of drugs that may keep a deadly form of skin cancer from becoming resistant to treatment.

The agent known as CelePlum-777 combines a special ratio of the drugs celecoxib, an anti-inflammatory, and plumbagin, a toxin. By combining the drugs, the cells have difficulty overcoming the effect of having more than one active ingredient. They work together to kill melanoma cells. Researchers used nanoparticles to deliver the drugs directly to the cancer cells-smaller than the width of a hair and can be loaded with medications.

This study was published in the March 2017 issue of Molecular Cancer Therapeutics.

“Loading multiple drugs into nanoparticles is one innovative approach to deliver multiple cancer drugs to a particular site where they need to act and have them released at that optimal cancer cell killing ratio,” said Raghavendra Gowda, PhD, assistant professor of pharmacology, who is the lead author on the study in a news release. “Another advantage is that by combining the drugs, lower concentrations of each that are more effective and less toxic can be used.”

Because of their toxicity, they are not delivered at the same time, or by mouth, only intravenously. The Penn State team showed that CelePlum-777 killed cancer cells growing in culture dishes and in tumors growing in mice following intravenous injection. The drug prevented tumor development in mice with no detectable side effects and also prevented proteins from enabling uncontrolled cancer cell growth. The drugs are so tiny, they burrow into the tumor cell and then are released.

"This drug is the first of a new class, loaded with multiple agents to more effectively kill melanoma cells, that has potential to reduce the possibility of resistance development," said senior author Gavin Robertson, PhD, professor of pharmacology, pathology, dermatology, and surgery; director of the Penn State Melanoma and Skin Cancer Center and member of Penn State Cancer Institute. This could be the next big breakthrough in melanoma treatment.

Human trials have not yet begun-the US Food and Drug Administration approval is pending additional research on toxicity.