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SOURCE: Dr. Shad C. Thaxton/Northwestern University

HDL nanoparticles inside a lymphoma cell: A lymphoma cell (left) has been treated with synthetic HDL nanoparticles.  The area outlined is observed at progressively higher magnification moving from left to right.  In the right panel, the gold nanoparticles at the core of the HDL nanoparticles become visible as dark black spots within the cell.

Road to cancer cure may be paved with gold

by Ajai Sreevatsan
Jan 29, 2013


SOURCE: Leo I. Gordon

The structure of natural HDL cholestrol

What do you do with cancer cells that extract nutrients from the body to help them grow? Well, feed them gold and see them choke.

That might seem like a strange solution. But it works.

A team at Northwestern University has killed cancerous lymphoma cells by feeding them gold nanoparticles that mimic a type of cholesterol called high-density lipoprotein.

The results of the study were published this month in the Proceedings of the National Academy of Sciences.

HDL, commonly known as “good cholesterol,” turns out to be the favorite food of cancerous lymphoma cells. The mutant cells eat voraciously and grow rapidly. But this craze for cholesterol comes at a price. Gold nanoparticles that resemble HDL in structure and appearance can easily deceive the cancer cells. They lock into the cell’s HDL receptors and starve them to death.

“The cell is looking for an influx of cholesterol, but it gets a mouthful of gold instead,” said Dr. Leo I. Gordon, an oncologist at Northwestern’s Feinberg School of Medicine.

Gordon and his colleague Dr. Shad Thaxton found that the synthetic nanoparticles killed B-cell lymphoma in cultured human cells and inhibited tumor growth in mice.

Lymphoma is cancer of the lymph nodes, hubs of the body’s immune system. B-cell lymphoma is the most common type of non-Hodgkin lymphoma, a disease that was reported in about 70,000 Americans in 2012, causing 19,000 deaths, according to the National Cancer Institute.

Gordon said that they were originally looking for novel ways to target cancer cells with chemotherapy drugs. But the researchers ended up discovering that the nanoparticle in isolation was as good at fighting cancer as its drug-laced counterpart.

“We were trying to find ways to target cancer drugs. In the process, we discovered a new drug,” Thaxton said.

That was not the only act of serendipity involved in the discovery. Thaxton is a urologist who reads textbooks on heart diseases. His interest in HDL lay in finding cures for cardiovascular diseases.  These blobs of “good cholesterol” scavenge on low-density lipoprotein, also known as “bad cholesterol”, and transport them to the liver where LDL can be reprocessed. Thus, the level of HDL is believed to determine the risk of heart disease.

“Gordon happened to be in a talk that I was giving,” Thaxton said. “He suggested we could use the synthetic particle to fight cancer instead. And lo and behold! The particle engaged lymphoma cells and ended up killing them.”

Khalid Salaita, a biochemist at Emory University in Atlanta, described the study’s finding as “immensely surprising.” These synthetic particles are hijacking the cell’s cholesterol mechanism, he said. “It’s essentially a Trojan horse that deceives the cancer cell.”

The use of nanoparticles seems to have resulted in some “impressive selectivity” as normal cells were left largely unharmed, Salaita said. “Nanoparticles enter the cell sometimes through surprising mechanisms. This study offers a blueprint for how the field of nanotechnology should use the field of biological understanding for therapeutic purposes,” he added.

However, both Gordon and Thaxton insist that these are “preliminary findings” and further trials are required. But in case it leads to a therapeutic drug, it could offer a way to treat lymphoma without subjecting patients to chemotherapy.

“The problem with chemotherapy is that it's not discriminatory,” Gordon said. “It is time to look beyond. Many tumor cells require nutrients and oxygen for their growth. It is an interesting area for cancer research.”