'C dots' light up tumors

David L. Shenkenberg, david.shenkenberg@laurin.com

When surgeons remove tumors, they cannot determine exactly where the cancer ends and the tissue begins, so they make educated guesses. If they could label the tumor with bright fluorescent molecules, such as quantum dots, they could cut out the cancerous tissue more precisely.

As a step toward fluorescently labeling tumors in cancer patients, researchers at Memorial Sloan-Kettering Cancer Center conducted imaging experiments with tumor-bearing mice using a variation of quantum dots that they call “C dots.” The researchers believe that the latter are in a class by themselves.

Shown are C dot fluorescent silica nanoparticles with cancer cells. Specifically, they are TAT-peptide conjugated C dots (red) taken up by mouse prostate cancer cells (membrane stained green). The scale bar is 20 μm. Courtesy of Andrew Burns and Ulrich Wiesner.

C dots, or Cornell dots, were developed in Ulrich Wiesner’s lab at Cornell University in Ithaca and modified at Sloan-Kettering. C dots are made of silica, a nontoxic material that is commonly found in fruits, grains and vegetables. The FDA classifies silica as a compound that is “generally regarded as safe.”

Before researchers such as Wiesner started using silica, quantum dots were made out of toxic materials including cadmium and lead because they were not originally designed for medical or biological purposes.

Wear ‘bathing suits’

Besides being safer than quantum dots, the C dots’ fluorescence is enhanced by the rigidity of the silica, a phenomenon not observed in quantum dots. The C dots have a core and shell of silica. In between the core and shell are fluorescent dyes. Wiesner compared the shell to a bathing suit. “Dyes usually hate water. We put them into a bathing suit which is silica and throw them back into water.” The dyes emit at longer wavelengths than commercially available fluorescent dyes, which enhances the image quality.

The C dots were 20 to 25 nm in diameter, but the researchers now can make them 5 nm. As reported in the January 2009 issue of Nano Letters, the small size of the 5-nm C dots enabled the particles to circulate throughout the bloodstream of mice for a reasonable amount of time and to be efficiently excreted through the urine.

Additionally, the particles are three times brighter than they were before. The researchers found that coating the surface of the C dots with polyethylene glycol protected them from being recognized and consumed by white blood cells, which attack matter that is foreign to the bodies of mice and men.

“Highly sensitive and specific probes and molecular imaging strategies are critical to ensure the earliest possible detection of a tumor and timely response to treatment,” said the study’s senior author Michelle Bradbury, MD, PhD.

Compared with other imaging techniques, such as MRI or PET, fluorescence is cheaper and employs smaller instruments that can be used at the point of surgery. Fluorescent molecules such as the C dots also can be targeted to specific tumor types, enabling physicians to see the extent of tumor blood vessels, the response to treatment, and the spread to lymph nodes and distant organs.

Wiesner said that they are modifying C dots to target specific tumors. The C dots also could be used to deliver drugs directly to tumors. However, it will be some time before they will be approved for use in humans.