Novel Therapeutic Device Zaps Cancer Cell

Researchers report important advances toward a therapeutic device that has the potential to capture cells as they flow through the blood stream and treat them. Among other applications, such a device could stop cancer cells spreading to other tissues, or signal stem cells to differentiate.

The investigators, from the Massachusetts Institute of Technology (MIT; Cambridge, MA, USA) and the University of Rochester (NY, USA), reported that their concept utilizes the mechanism of cell rolling, a biologic process that slows cells down as they flow through blood vessels. As the cells slow, they adhere to the vessel walls and roll, allowing them to sense signals from neighboring tissues that may be signaling them to work. Immune cells, for example, can be slowed and summoned to fight an infection.

"Through mimicking a process involved in many important physiological and pathologic events, we envision a device that can be used to selectively provide signals to cells traveling through the bloodstream,” said Dr. Jeffrey M. Karp, from the Harvard University- (Cambridge, MA, USA)-MIT Division of Health Sciences and Technology. "This technology has applications in cancer and stem cell therapies and could be used for diagnostics of a number of diseases.”

The team, led by Dr. Karp, started with technology to induce cell rolling for research. With an implantable therapeutic device in mind, they improved that cell rolling technology to make it safe, more stable, and longer lasting. The improvements were described in the October 20, 2007, online issue of the journal Langmuir published by the American Chemical Society.

In the body, P-selectin and other selectin proteins regulate cell rolling in blood vessels. When P-selectin is present on a vessel's inner wall, cells that are sensitive to it will stick to that patch and begin to roll across it. To induce rolling in the laboratory, the original technology weakly adheres P-selectin to a glass surface and flows cells across it. This surface treatment remains stable for several hours then breaks down. "While this method is useful for experiments, it's not good for long-term stability,” stated Dr. Karp. An implantable device needs a coating that lasts weeks or even months so that patients do not need to come in frequently for replacements.

To improve the technology, the team experimented with several chemical methods to immobilize P-selectin on a glass surface. They identified a polyethelene glycol (PEG) coating that strongly bonded to P-selectin. This coating is also non-fouling,” meaning it does not react with or accumulate other proteins, so it is potentially safe for use in an implant.

P-selectin remains stable on this coating for longer than the original technology. In tests with microspheres coated with a molecule that interacts with P-selectin, these spheres slowed down considerably as they flowed over the surface coated with layers of PEG and P-selectin. The effect was stable past four weeks, the longest the devices have been tested.

To confirm that this technology works with cells sensitive to P-selectin, the researchers flowed neutrophils (the most abundant type of white blood cells) across the coated surface. In addition, they slowed and rolled on surfaces treated with the new coating, and the effect again lasted for at least four weeks. The next step will be converting these findings to animal studies and using the technology to slow and capture stem cells and cancer cells circulating in the blood stream.

Ultimately, CellTraffix, Inc. (Pittsofrd, NY, USA), a sponsor of this technology and its licensee, wants to apply the technique to a device that is either implanted into the blood stream or appended as a shunt. In addition to PEG and selectin molecules, the device would also include a therapeutic agent. Such an agent would interact only with certain cells for a specific purpose.

According to University of Rochester biomedical engineering professor Dr. Michael King, who developed the concept for adhesive capture and reprogramming of cells, the device could, for example, slow down metastatic cancer cells and kill them.


Related Links:
Massachusetts Institute of Technology
University of Rochester
CellTraffix