A Bright New Method for Rapidly Screening Cancer Drugs

Illustration of red, green and blue fluorescent proteins.
Chemists have devised a new approach to screening cancer drugs that uses gold nanoparticles with red, green and blue outputs provided by fluorescent proteins. Credit: University of Massachusetts Amherst.

Scientists may screen billions of chemical compounds before uncovering the few that effectively treat a disease. But identifying compounds that work is just the first step toward developing a new therapy. Scientists then have to determine exactly how those compounds function.

Different cancer therapies attack cancer cells in distinct ways. For example, some drugs kill cancer cells by causing their outer membranes to rapidly rupture in a process known as necrosis. Others cause more subtle changes to cell membranes, which result in a type of programmed cell death known as apoptosis.

If researchers could distinguish the membrane alterations of chemically treated cancer cells, they could quickly determine how that chemical compound brings about the cells’ death. A new sensor developed by a research team led by Vincent Rotello of the University of Massachusetts Amherst can make these distinctions in minutes.

The sensor consists of blue, green and red fluorescent proteins bound to a gold nanoparticle. While attached to the nanoparticle, the proteins lose their ability to fluoresce. When the scientists add the sensor to cancer cells treated with a chemical compound, the nanoparticles attach to the cells’ membranes and shed some of their fluorescent proteins. The exact proportion of each of the three types of protein released depends on the strength of attraction between the nanoparticle and the cell, which varies according to how each compound affects the cell membrane. Once released from the nanoparticle, the proteins fluoresce again, displaying unique patterns of colored light for distinct methods of cell death.

Using this sensor, the scientists identified light patterns broadly associated with apoptosis and necrosis, as well as with more specific mechanisms of cell death within each of those groups. They found that their sensor was effective at distinguishing the mechanisms of individual drugs as well as combination therapies involving multiple drugs.

In a recent news release, Rotello said, “In addition to drug screening, the simplicity and speed of this…technology holds the promise to greatly accelerate the search for effective cancer treatments, and provides a step forward in areas such as toxicology, where the safety of thousands of uncategorized chemicals needs to be assessed.”

This work was funded in part by NIH under grant R01GM077173.