Outwitting chemoresistant ovarian cancer with nanoparticle treatment

Women diagnosed with ovarian cancer may initially respond well to chemotherapy, but the majority will develop resistance to the treatment and die from the disease. Now, Northwestern Medicine scientists have discovered the Achilles heel of chemotherapy-resistant ovarian cancer – its craving for cholesterol – and how to sneakily use it to destroy it.

Their findings are published in the journal Advanced science.

In the new study, scientists showed for the first time that chemotherapy-resistant ovarian cancer cells and tumors are rich in cholesterol due to increased absorption of it. They then deployed a synthetic nanoparticle that appeared to cancer cells like a natural cholesterol-rich nanoparticle.

But when the cancer cells bound to the fake particle, it actually blocked the absorption of cholesterol. Additionally, scientists showed that lowering cholesterol tricked cancer cells into cell death. Treatment with the nanoparticle reduced the growth of ovarian tumors by more than 50% in human cells and animal models.

“This is a new weapon to destroy resistant ovarian cancer,” said co-corresponding author C. Shad Thaxton, associate professor of urology at the Feinberg School of Medicine at Northwestern University. .

“More than 18,000 women die from ovarian cancer each year,” said co-corresponding author Dr. Daniela Matei, professor of medicine at Northwestern University Feinberg School of Medicine and Northwestern Medicine oncologist. “It is very important to find new ways to attack resistant cancer cells.”

Matei and Thaxton show that the way cells die after treatment with these nanoparticles is a form of cell death executed by oxidation of cell membrane lipids.

“These cancer cells are resistant to the typical form of death, apoptosis, which is why chemotherapy cannot kill them,” Matei said.

The ovarian cancer findings build on previous preclinical research by Thaxton and Dr. Leo Gordon using nanoparticles to treat lymphoma.

The new study showed that the approach also works in ovarian cancer cells.

Matei and Thaxton tested the nanoparticles in ovarian cancer cells and in animals carrying chemotherapy-resistant ovarian cancer xenografts. The next step in the research is to test a combination of particles with traditional chemotherapy and study the effects of the nanoparticles on immune cells that fight cancer.