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Heat, Iron-Oxide Nanoparticles Improve Cancer Drug Delivery

Oleh Taratula

Oleh Taratula (Oregon State University)

Pharmaceutical and engineering researchers at Oregon State University in Corvallis developed a technique with heated iron-oxide nanoparticles that in lab tests was shown to kill ovarian cancer cells with chemotherapy drugs. The team led by Oregon State pharmacy professor Oleh Taratula published its findings this month in an advance online paper in the International Journal of Pharmaceutics.

The Oregon State researchers, from Taratula’s lab and colleagues from the lab of engineering professor Pallavi Dhagat, along with nanomaterials company Ocean Nanotech, addressed a problem with treatments for ovarian cancer, a condition that affects 12.5 in every 100,000 women in the U.S., and is expected to cause more than 14,000 deaths this year. Because ovarian cancer is often diagnosed in advanced stages, treatment requires both surgery and chemotherapy. And while initial chemotherapy may be successful, cancer may recur in up to 75 percent of cases, leading to a resistance to chemotherapy drugs.

The technique tested by the researchers aimed to improve the targeting and effectiveness of chemotherapy drugs, particularly with the addition of heat. Higher temperatures have been known to improve the efficacy of cancer drugs, but heating only cancer cells and not surrounding tissue cells, which can lead to dangerous side effects, is difficult to achieve.

The test methods use nanoscale particles — 1 nanometer equals 1 billionth of a meter — of iron oxide coated with the chemotherapy drug doxorubicin, marketed under the brand names Doxil, Adriamycin, and Rubex. The team engineered the nanoparticles to an average size of 97 nanometers considered optimal for stability in the body and to reduce the chance of rejection by the immune system.

Nanoparticles were also coated with polyethylene glycol, an organic polymer compound to prevent clumping and initially protect them from the acidic environment often found in tumors. The particles had an additional coating, of luteinizing hormone-releasing hormone, a peptide with an affinity for cancer cells to improve targeting.

As Dhagat explains in a university statement, the researchers heated the particles with an alternating magnetic field, where, the iron oxide absorbs energy from the magnetic field raising their temperature. The particles, in this case, were heated to a temperature of 40 degrees C (104 F).

In lab tests, the team found the heated, coated nanoparticles killed 95 percent of the sample ovarian cancer cells. The researchers say doxorubicin by itself killed 27 percent of the cancer cells, while heating alone generated by the nanoparticles killed 72 percent of the cancer cells.

“Cancer is always difficult to treat,” says Taratula, “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.” He says tests with animals will come next and eventually human clinical trials.

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