Texas Medical Center

Drug Delivery System Targets Ovarian Tumors


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SPECIAL DELIVERY—Mauro Ferrari, Ph.D., who heads The Methodist Hospital Research Institute, worked with fellow scientists to develop tiny nanoparticles that maneuver through the bloodstream to carry cancer-battling drugs to tumors. (Photo by Matt Landry)

 

By David Bricker  |  The Methodist Hospital

Researchers at The Methodist Hospital, The University of Texas MD Anderson Cancer Center, and Weill Cornell Medical College have found a new way to deliver cancer drugs that can reduce the size of ovarian tumors by as much as 83 percent. In addition, the drug delivery system can stop tumor growth in ovarian cancer tissue that is resistant to chemotherapy.

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Upon arriving at a cancerous tumor, a
nanoparticle releases drugs that will
bind  to the tumor and fight the cancer.

Their study, conducted in mice, is published online and will be featured in an upcoming issue of the journal Clinical Cancer Research.

“Drug resistance is a huge problem,” said Mauro Ferrari, Ph.D., president and CEO of The Methodist Hospital Research Institute and one of the senior authors of the paper. “New approaches to overcoming drug resistance are urgently needed to improve the survival of cancer patients.”

To address this problem, the research team decided to use a weapon known as small inhibitory RNA – a snippet of genetic material that interferes with the expression of genes, in this case, a gene that plays a major role in ovarian cancer.

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Anil Sood, M.D.

This approach to fighting ovarian cancer was developed by Anil Sood, M.D., of MD Anderson’s gynecologic oncology and reproductive medicine department, and Gabriel Lopez-Berestein, M.D., of MD Anderson’s experimental therapeutics department. Their intent was to use small inhibitory RNA to stop the cancer cells from growing, and eventually kill them.

But small inhibitory RNA can’t simply be injected into a patient. It’s very fragile, and enzymes in the blood and inside cells would destroy the RNA before it could reach the cancer cells.

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Gabriel Lopez-
Berestein, M.D.

So MD Anderson researchers clad the small inhibitory RNA in a protective cloak made of fat cells. Still, this wasn’t good enough. Most of the RNA didn’t last very long in the blood.

So Ferrari’s group at Methodist developed disc-shaped nanoparticles made of silicon that bind to the outside of cancer cells. The researchers then put the small inhibitory RNA, cloaked in fat cells, inside Ferrari’s silicon nanoparticles, injected them into the mice, and like tiny disc-shaped submarines, off they went to battle ovarian cancer.

Over the next six weeks, twelve injections of 15 micrograms of nanoparticles appeared to reduce the ovarian tumors by 83 percent.

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Haifa Shen,
M.D., Ph.D.

Then researchers decided to take it a step further. They added the common chemotherapy drug paclitaxel, trade names Taxol and Onxal, inside the nanoparticles. With the drug added, the researchers saw zero tumor growth. Furthermore, the existing tumors began to disappear.

“We can completely eliminate tumor nodules, which means the patients – in this case, mice – can achieve long-term survival,” said research team member Haifa Shen, M.D., Ph.D., with Methodist’s research institute. The next step is to test the therapy in humans.

“We will be contacting the Food and Drug Administration to work out a road map designed to get us to clinical trials,” Shen said.