Circulating tumor cells (CTCs), shed into the blood stream by tumors, are thought to provide a means of detecting cancer early, conducting a preliminary assessment of which anticancer agents might prove most effective at treating a given patient, and assessing whether a chosen therapy is working. But, to realize that potential, it is first necessary to detect and trap these rare cells in a fast, efficient, and reliable manner—something that researchers are getting close to accomplishing. In fact, a new research paper from investigators at Emory and Georgia Tech, published in the journal Cancer Research, highlights one promising method that uses gold nanoparticles to detect the presence of CTCs in human blood samples.
One challenge with detecting CTCs is separating out signals from white blood cells, which are similarly sized as tumor cells and can stick to the same antibodies normally used to identify tumor cells. Commercially available devices trap CTCs using antibody-coated magnetic beads, and technicians must stain the trapped cells with several antibodies to avoid falsely identifying white blood cells as tumor cells.
The Emory and Georgia Tech team, led by Dr. Shuming Nie and Dr. Dong Shin, have now shown that polymer-coated and dye-studded gold particles, directly linked to a growth factor peptide rather than an antibody, can detect circulating tumor cells in the blood of patients with head and neck cancer.
"The key technological advance here is our finding that polymer-coated gold nanoparticles that are conjugated with low molecular weight peptides such as EGF [epidermal growth factor] are much less sticky than particles conjugated to whole antibodies," said Nie. "This effect has led to a major improvement in discriminating tumor cells from non-tumor cells in the blood."
EGF binds to the epithelial growth factor receptor (EGFR) that is over-produced on the surfaces of several types of tumor cells.
Upon laser illumination, the particles display a sharp fingerprint-like pattern that is specific to the dye, because the gold enhances the signal coming from the dyes. These results suggests that several types of nanoparticles, each designed to bind to a specific tumor-related molecular marker, could be combined to gain more information about the growth characteristics of the tumor cells. In addition, measuring CTC levels may be sensitive enough to distinguish patients with localized disease from those with metastatic disease.
"Nanoparticles could be instrumental in modifying the process so that circulating tumor cells can be detected without separating the tumor cells from normal blood cells," Nie said. "We've demonstrated that one tumor cell out of approximately one to ten million normal cells can be detected this way."
In collaboration with oncologists at Winship Cancer Institute, the Emory and Georgia Tech team used their nanoparticles to test for CTCs in blood samples from 19 patients with head and neck cancer. Of these patients, 17 had positive signals for CTCs in their blood. The two with low signals were verified to have no circulating cells using a different CTC-detection technique.
"Although the results have not been compared or validated with current CTC detection methods, our 'one-tube' SERS technology could be faster and lower in costs than other detection methods," said Shin, who is the director of the Winship Cancer Institute Chemoprevention Program. "We need to validate this pilot study by continuing with larger groups of patients and comparing with other tests."
This work, which is detailed in a paper titled, "Detection of Circulating Tumor Cells in Human Peripheral Blood using Surface-Enhanced Raman Scattering Nanoparticles," was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis and treatment of cancer. An abstract of this paper is available at the journal's website. At the time this research was conducted, Dr. Nie was the co-principal investigator of the Emory-Georgia Tech Center for Cancer Nanotechnology Excellence.