Research May Aid Cancer Diagnosis

October 1, 2003

Research May Aid Cancer Diagnosis

EVANSTON, ILL.— Scientists at Northwestern University have developed an ultra-sensitive technology based on gold nanoparticles and DNA that can detect prostate specific antigen (PSA) when present at extremely low levels in a blood sample. This promising new protein-detection method could be used to monitor prostate cancer patients following surgery and detect the early signs of breast cancer.

Prostate cancer in men and breast cancer in women are the second leading causes of cancer deaths in the United States. (Only lung cancer is more deadly.) The life-saving potential of early detection has been well established for years, and improved cancer screening methods have helped to reduce the threat.

The researchers have demonstrated that their method is a million times more sensitive than conventional methods, a feature that promises to change dramatically the way proteomics (the study and analysis of protein structure and function) and medical diagnostics are done. The results are published in the Sept. 26 issue of the journal Science.

“The polymerase chain reaction, which duplicates DNA so it can be analyzed, revolutionized forensics, medicine and biotechnology,” said Chad A. Mirkin, PhD, director of Northwestern’s Institute for Nanotechnology, who led the research team, “but we haven’t had anything of comparable sensitivity for proteins. Now we do. This technology will change the way we do cancer diagnostics and treatment.”

Biomarkers, like PSA, are known for hundreds of diseases. Using these protein targets, the new method could detect diseases at earlier stages than is possible now. For example, if disease should return in a prostate cancer patient after surgery, Dr. Mirkin’s method could detect the rise in PSA early on. Also, PSA is found in extremely low concentrations in breast cancer patients, requiring an ultrasensitive screening test for effective detection.

Because proteins, unlike DNA, cannot be chemically duplicated yet, the Northwestern researchers had to develop a method of signaling the presence of a protein. They chose to use DNA as their signal because it can be amplified and read using a number of methods.

Using commercially available materials, the team outfitted a magnetic microparticle and a gold nanoparticle each with the antibody of the protein target, PSA. When in solution, the antibodies “recognize” and bind to PSA, sandwiching the protein between the two particles.

The key is that attached to each tiny gold nanoparticle (just 30 nanometers in diameter) are hundreds to thousands of identical strands of DNA. Dr. Mirkin calls this “bar-code DNA” because they have designed it as a label specific to the protein target. After the “particle-protein-particle” sandwich is removed magnetically from solution, the DNA is removed from the sandwich and read using standard DNA detection methodologies.

In the experiments conducted by Dr. Mirkin’s team, the amount of PSA present was calculated based on the amount of bar-code DNA. The researchers detected approximately 20 PSA molecules in a 10-microliter sample, an illustration of the method’s extraordinary sensitivity.

“For each molecule of captured PSA, thousands of DNA strands are released, which is our way of amplifying the signal for a protein target of interest,” said Dr. Mirkin, also George B. Rathmann Professor of Chemistry. “Power exists in its simplicity. Instead of detecting PSA our method detects the DNA, which gives us a substantial increase in the signal.”

Using the new method, a test could be developed for any protein target with a known antibody. A unique “bar-code DNA” label can be created for each target. The technology could be commercially available in two years.

In addition to Dr. Mirkin, other authors on the Science paper are Jwa-Min Nam and C. Shad Thaxton, from Northwestern University. The research was supported by the Air Force Office of Scientific Research, Defense Advanced Research Projects Agency, and National Science Foundation.