ATLANTA – Pancreatic and ovarian cancers are two of the deadliest forms of cancer, primarily due to the fact that they aren't diagnosed until late stages. Nanotechnology may offer some early detection solutions and the latest advances were reported this week at BIO 2009, the annual meeting of the Biotechnology Industry Organization (Washington).

A range of strategies were presented as part of a panel discussion, from more sensitive imaging methods to molecular diagnosis and the integration of bioinformatics to accelerate targeted drug therapies. Two of the most highly regarded nanomedicine researchers – both based in Georgia – presented updates on their work.

Gang Bao, PhD, College of Engineering Distinguished Professor, Georgia Institute of Technology (Atlanta), and Shuming Nie, PhD, director, Cancer Nanotechnology Center, Emory University School of Medicine (Atlanta), pointed out that nanomedicine research will have the most immediate impact on diagnostics.

"The low-hanging fruit is in serum or in vitro diagnostics," Nie said.

"Almost every day I operate on somebody with ovarian cancer and almost all of them need chemotherapy," said Benedict Benigno, MD, CEO/founder, Ovarian Cancer Institute (Atlanta). "Unfortunately the tumor is spread throughout the abdominal cavity by the time it's diagnosed. We are limited in the use of chemotherapeutic drugs by the body's capacity to tolerate the poisons. There is no way to screen for ovarian cancer.

"Will we burn, slash and poison our way through another century?" Benigno asked, referring to current treatments: radiation, surgery and chemotherapy.

Not if researchers like Nie and Bao have their way.

Nie's lab is developing, among other things, quantum dots, which are light-emitting semiconductor crystals, that will be used to provide multicolor biomedical imaging at the nanoscale. The idea is to be able to spot cancer when it's very small.

"One of the applications of quantum dots is in vitro diagnostics for cancer," Nie said. "The ability to have multiple colors of quantum dots gives you the ability to profile multiple protein biomarkers simultaneously on the same specimen," he said, showing a standard immunohistochemistry slide next to a full-color version. Seeing a whole spectrum of colors – with red highlighting the cancer – was a much easier way to spot cancerous cells compared to gradations of white to black, even for untrained eyes.

"Even if there's a single malignant cell, we can reliably detect it with quantum dots," he said. "If you look at some of the complex sites in the tissue, the standard technology is a very heterogenous complex; you can get much information. If you do the multicolor quantum dot staining, the malignancies are predominant."

In addition to ovarian cancer, Nie said the quantum dot research work is being applied for prostate, pancreatic, lung and breast cancers. A spinout company, DiagNano (Atlanta), was formed three years ago to commercialize the dots (MDD, Oct. 3, 2008).

Projects at the fore of Bao's lab include the development of molecular beacons for use in real-time visualization of RNA expression and localization in living cells. Bao is developing nanoprobes for sensitive RNA detection in living cells, including dual FRET molecular beacons, peptide-linked molecular beacons and other activatable probes.

So far his team has proven that the dual-FRET molecular beacons approach is more effective in detecting mRNAs compared with single, unpaired molecular beacons.

"Another interesting application is to use molecular beacons to isolate stem cells from tumors and analyze them in order to develop new drug molecules," Bao said. "There are only a few stem cells in a tumor – one to 10 per 1 million cancer cells, so you need a very sensitive method to detect cancer stem cell markers. We designed a molecular beacon targeting a particular kind of cancer stem cell to do this.

"Molecular beacons can detect stem cell mRNA markers in live cancer stem cells with high specificity. It has the potential to detect cancer stem cells in tumor cells," Bao said.

Joe Beechem, PhD, chief technology officer at Invitrogen (Carlsbad, California), talked about the non-imaging application of quantum dot-based technology, specifically to develop digital based assays for the lab.

"Most assays today are analog based. Digital is far more sensitive than analog," he said. "The sensitivities are different. Quantum dots absorb a great deal of light and make single molecule work very easy to do, allowing for digital based assays. Digital counting diagnostics will change everything."