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January 23, 2013

Road to Lymphoma Cure Could be Paved with Gold

by Matthew Hilburn

A nanoparticle with a heart of gold could end up being enemy number one for lymphoma, and perhaps other types of cancer.

A new study shows that synthetic HDL nanoparticles with gold at their core can kill B-cell lymphoma, the most common form of lymphoma, in cultured human cells. The study, conducted by C. Shad Thaxton, M.D. and Leo I. Gordon, M.D., both of Northwestern University’s Feinberg School of Medicine, also showed that the nanoparticles inhibited B-cell lymphoma tumor growth in mice.

The concept behind the science works like this: Lymphoma cells love to eat
cholesterol delivered to the cell by HDL. When the cells attach to the synthetic HDL nanoparticles, thinking they’re going to tuck into a big meal, the trap is sprung. The spongy surface of the nanoparticle sucks cholesterol out of the lymphoma cell and, in a devastating blow, the gold nanoparticle core prevents the cancer cell from acquiring the cholesterol-rich meal at the core of natural HDLs, thus starving it to death.

This could mean future victims of lymphoma may be spared agonizing chemotherapy commonly administered today.

When the particle has done its job, Thaxton said, preliminary data in mice show that the nanoparticles appears to be metabolized through the liver, and eventually passed out through feces.

The notion of using the nanoparticle to fight cancer was born of pure luck.

In 2010, Thaxton, who originally intended for the nanoparticle to be used against heart disease, was giving a lecture on his project. Gordon, a professor of hematology/oncology was in the audience. Gordon knew that patients with advanced forms of B-cell lymphoma sometimes show decreasing levels of cholesterol. He contacted Thaxton and they began to collaborate.

They tested the HDL nanoparticle as a delivery mechanism for cancer drugs and the nanoparticle alone. Surprisingly, the nanoparticle without drugs was just as effective at killing the B-cell lymphoma cells.

"We thought, 'That's odd. Why don't we need the drug?'" Gordon recalled.

Thaxton said human trials are at least two years away, as the treatment will have to pass the standard hurdles set by the Food and Drug Administration before it is approved for use on people.

While gold prices have been soaring in recent years, Thaxton doesn’t see the treatment becoming prohibitively expensive.

“The cost of the material is very low because the particles are so small,” he said.  Each cholesterol particle uses a 5 nanometer diameter gold particle.

Thaxton hopes the treatment could be effective against other cancers as well.

“We’re just initiating that research,” he said. “In the paper, we show there are other [cancer] cell types that have the receptors for HDLs, which leads us to believe there may be other cancers that would respond.”

The National Cancer Institute reports that in 2012 there were about 70,000 new cases of non-Hodgkin lymphoma in the U.S. and nearly 19,000 deaths. About 90 percent of those new cases were B-cell lymphoma.

Thaxton added that potential uses of the nanoparticles to fight heart disease are also being explored.

The researchers’ paper was published January 21 in the journal Proceedings of the National Academy of Sciences.