First Genetic-Based Tool To Detect Circulating Cancer Cells In Blood

NanoFlares-specially designed stem cells that have been
developed to detect blood-borne cancers. When the cells come in
 contact with cancerous cells, they emit light. (Credit: International
Institute for Nanotechnology at Northwestern University)
Metastasis is bad news for cancer patients. Scientists have now demonstrated a simple but powerful tool that can detect live cancer cells in the bloodstream, potentially long before the cells could settle somewhere in the body and form a dangerous tumor.
The NanoFlare technology is the first genetic-based approach that is able to detect live circulating tumor cells out of the complex matrix that is human blood. In a breast cancer study, the NanoFlares easily entered cells and lit up the cell if a biomarker target was present, even if only a trace amount. The NanoFlares are tiny spherical nucleic acids with gold nanoparticle cores outfitted with single-stranded DNA "flares".
The research team, in a paper published in the Proceedings of the National Academy of Sciences (PNAS), reports two key innovations:
- The ability to track tumor cells in the bloodstream based on genetic content located within the cell itself, as opposed to using proteins located on the cell's surface (current technology)
- The ability to collect the cells in live form, so they may be studied and used to inform researchers and clinicians as to how to treat a disease -- an important step toward personalized medicine
A NanoFlare is designed to recognize a specific genetic code snippet associated with a cancer. The core nanoparticle, only 13 nanometers in diameter, enters cells, and the NanoFlare seeks its target. If the genetic target is present in the cell, the NanoFlare binds to it and the reporter "flare" is released to produce a fluorescent signal. The researchers then can isolate those cells.
Once they identified the cancer cells, the researchers were able to separate them from normal cells. This ability to isolate, culture and grow the cancer cells will allow researchers to zero in on the cancer cells that matter to the health of the patient. Most circulating tumor cells may not metastasize, and analysis of the cancer cells could identify those that will.
In the study, the genetic targets were messenger RNA (mRNA) that code for certain proteins known to be biomarkers for aggressive breast cancer cells.
The research team first used the blood of healthy individuals, spiking some of the blood with living breast cancer cells to see if the NanoFlares could detect them. (Unspiked blood was used as a control.)
The research team tested four different NanoFlares, each with a different genetic target relevant to breast cancer metastasis. The technology successfully detected the cancer cells with less than 1 percent incidence of false-negative results.
Currently, in another study, the researchers are focused on detecting circulating tumor cells in the blood of patients with a diagnosis of breast cancer.