May 11, 2005 issue of Nano Letters -----
Binding gold nanoparticles to a specific antibody for cancer cells could make cancer detection much easier, say medical researchers from the University of California, San Francisco and Georgia Institute of Technology.
The researchers are a father and son, working together on opposite coasts. Their study findings are reported in a recent edition (May 11) of the journal Nano Letters, published by the American Chemical Society.
Principal author is Ivan El-Sayed, MD, assistant professor of otolaryngology at UCSF Medical Center, who conducted the study with his father, Mostafa El-Sayed, PhD, director of the Laser Dynamics Laboratory and chemistry professor at Georgia Tech.
“Gold nanoparticles are very good at scattering and absorbing light,” said Mostafa. “We wanted to see if we could harness that scattering property in a living cell to make cancer detection easier. So far, the results are extremely promising.”
Many cancer cells have a protein, known as epidermal growth factor receptor (EFGR), all over their surface, while healthy cells typically do not express the protein as strongly. By conjugating, or binding, the gold nanoparticles to an antibody for EFGR, suitably named anti-EFGR, the researchers were able to get the nanoparticles to attach themselves to the cancer cells.
“After we added the nanoparticle-bound antibody to cells, using a simple technique known as darkfield microscopy, we saw the cancer cells light up under the microscope,” said Ivan. “The healthy cells don’t bind the particles well and are dark compared to the cancer. Since the particles have color, we can test multiple antibodies at the same time with a white light. Using simple optics, we can develop low cost techniques for rapid automated detection of cancer in biopsies. Further, we hope to use the scattering and absorption properties to develop techniques to detect cancer in humans without a biopsy.”
In the study, the research team found that the gold nanoparticles have 600 percent greater affinity for cancer cells than for noncancerous cells. The researchers tested their technique using cell cultures of two different types of oral cancer and one nonmalignant cell line. They found two features of the particles to be useful for cancer detection. First, with a microscope, they could see the cells shining. Second, they could measure changes in the amount of light absorbed by the particle as the antibody bound to its target.
According to Ivan, the changes in absorption may be particularly useful in cancer and cell research to measure molecules interacting inside living cells. The change in the absorption spectrum of the gold nanoparticles is also found to distinguish between cancer cells and noncancerous cells. Since nanoparticles of different shapes and sizes absorb and scatter light differently, multiple color probes can be made which may detect many molecules at the same time.
What makes this technique so promising, the researchers explained, is that it doesn’t require expensive high-powered microscopes or lasers to view the results, as other techniques require. All it takes is a relatively simple, inexpensive microscope and white light.
Another benefit is that the results are instantaneous. “If you take cells from a cancer stricken tissue and spray them with these gold nanoparticles that have this antibody, you can see the results immediately. The scattering is so strong that you can detect a single particle,” said Mostafa.
Finally, the technique isn’t toxic to human cells. A similar technique using artificial atoms known as quantum dots uses semiconductor crystals to mark cancer cells, but the semiconductor material is potentially toxic to the cells and humans.
“The wonderful thing about colloidal gold is that it has been used in humans for 50 years,” Ivan said. “For example, a radioactive form of it has been used to search for cancer and we know how it is handled by the body.”
“This technique is very simple and inexpensive to use,” said Ivan. “We think it holds great promise in making cancer detection in humans and under the microscope easier, faster and less expensive.”
While the technique is not ready to be used in patients, Ivan said it holds much promise for oral cancer patients he treats in his practice at UCSF Medical Center. “Oral cancer is deadly and tends to recur. Our best chance to save lives is to catch it early, and this method might allow that.” He added that this technique could be used to detect a number of cancers, including stomach, colon and skin cancers.
“Our findings also have strong implications for this technique’s value to cancer research,” Ivan added. “By watching the particle change colors in living cells we can identify molecular interactions within the cells. This may help us unravel the inner workings of a cancer cell and produce better treatments. The fact that we can see one particle is exciting.”
The research was supported by a grant from the Chemical Science, Geoscience and Biosciences Division of the U.S. Department of Energy.