Cellular Heating, Nanotech System Developed to Improve Ovarian Cancer Treatment

The findings, up to now only performed in a laboratory environment, reveals that this combination of mild hyperthermia and chemotherapy can kill 95% of ovarian cancer cells, and scientists reported that they expect to improve on those results in continued research.

The research is important, the researchers noted, because ovarian cancer, a leading causes of cancer-related deaths in women, frequently develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women worldwide every year. “Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery,” said Dr. Oleh Taratula, an assistant professor in the OSU College of Pharmacy. “It’s essential for the chemotherapy to be as effective as possible the first time it's used, and we believe this new approach should help with that.”

Elevated temperatures are known to help kill cancer cells, but heating just the cancer cells is problematic. The new system incorporates the use of iron oxide nanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell. Other features have also been developed to optimize the new system, in a unique collaboration between material science specialists, engineers, and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size so the immune system will not reject it. A customized polyethylene glycol coating additionally adds to the “stealth” effect of the nanoparticles and keeps them from clumping up, and the interaction between the cancer agent and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

“The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field,” said Dr. Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. “The nanoparticles absorb energy from the oscillating field and heat up.”

The result, in laboratory tests with ovarian cancer cells, was that a slight dose of the chemotherapeutic drug, combined with heating the cells to about 45 °C, destroyed nearly all the cells and was much more effective than either the drug or heat this research would leave approximately 70% of the cancer cells alive. With this new strategy, only 5% were still viable.

The research was published October 2013 in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech (Springdale, AR, USA).

“I’m very excited about this delivery system,” Dr. Taratula said. “Cancer is always difficult to treat, and this should allow us to use lower levels of the toxic chemotherapeutic drugs, minimize side effects, and the development of drug resistance, and still improve the efficacy of the treatment. We’re not trying to kill the cell with heat, but using it to improve the function of the drug.”

Iron oxide particles had been used before in some medical treatments, according to the researchers, but not with the complete system developed at OSU. Animal tests, and eventually human trials, will be needed before the new system is available for use. Drug delivery systems such as this may later be used in other forms of cancer, such as prostate or pancreatic cancer, to help improve the effectiveness of chemotherapy in those disorders, according to Dr. Taratula.

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Oregon State University
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