Testing nanoparticles

Testing nanoparticles for toxic effects could become faster and cheaper with a new highly mechanized technique described online in Proceedings of the National Academy of Sciences.

Several types of nanometer-sized particles are now approved for medical use, including magnetic nanoparticles to enhance contrast in imaging techniques such as MRI. Researchers are also experimenting with nanoparticles that could better target a drug to a specific part of the body, among other applications.

But nano-sized particles often interact in unpredictable ways with biological molecules and cells. Before a new medical product can be approved, it has to undergo lengthy and expensive trials, first in lab dishes and then in animals and humans, to test for possible toxic effects as well as efficacy.

Stanley Shaw of Massachusetts General Hospital in Boston and his collaborators have now devised a technique to identify promising new nanoparticles before testing them in animals. The researchers place dozens of different cell types — taken from different tissues and organs — on a petri dish that has hundreds of small, separate wells. Next, a robotic arm deposits 50 types of nanoparticles into the wells, so that the nanoparticles will interact with the cells in all possible combinations.

The researchers then virtually take the cells’ pulse. They monitor different signs of cell metabolism, such as the activity of mitochondria, the organelles that produce the cell’s energy.

This method differs from typical toxicology experiments on nanoparticles that just test whether cells live or die, Shaw says. “It’s an early proof of principle for a new concept.” The idea is reminiscent of the brute-force testing of the interactions of hundreds of compounds at once with biological molecules, in the hope of identifying potential new drugs.

Shaw says the technique can identify new particles whose effects on cells are similar to those of particles that are known to be safe. The method makes it easier to identify a few candidates to test in animals. “There’s no substitute for a living organism” to test if a material is toxic, Shaw says.

Chemist Mark Wiesner of DukeUniversity in Durham, N.C., says the researchers’ approach is ambitious in its scope. “You have to take your hat off to anyone who launches into this kind of study,” he says. However, Wiesner adds that he would also like to see the nanoparticles, not just the cells, analyzed after the experiment. That would reveal more detail about the possible toxicity of a nanoparticle, since some nanoparticles may be more or less toxic depending on what molecules they are interacting with. The way nanoparticles interact with cells is highly dependent on the way they bind with biological molecules, he says.