A nanovalve that opens in response to pH changes could let a high-tech pill target diseased tissue. By filling a tiny, silica sphere with a drug and then plugging its pores with the valves, researchers can use pH changes to control the drug's release.

The pH of healthy and specific tissue often differs, so the spheres could be designed to only release the drug in diseased tissue, says J. Fraser Stoddart, professor of chemistry at Northwestern University. Stoddart, along with UCLA chemistry professor Jeffrey Zink, led development of the new nanovalve.

Previous versions worked with only organic solvents and were activated by elaborate oxidation reactions. Switching to a pH-activated mechanism lets the valve work in water, a critical feature for any drug-delivery system. “We're now putting a lot of emphasis on biocompatibility,” says Stoddart.

At just 400-nm diameter, says Stoddart, the spheres would easily be taken up by cells. Once inside, they would respond to the cells' pH and either retain or release their contents.

The plug molecule, called a cucurbituril, binds to a molecular stalk by electrostatic forces in acidic pH fluid, keeping the plug in place. But when the pH turns basic, forces are disrupted, and the plug comes off its molecular stalk. Drugs are then free to leak out of the spheres.

Researchers are also experimenting with other mechanisms for triggering a drug's release. For example, diseased cells might emit a particular enzyme not present in healthy counterparts. “If we can use the enzyme, specifically in a diseased cell, to break a particular chemical bond, then we can introduce that chemical bond on the sphere,” says Stoddart.

He hopes to deploy the pills for cancer treatments, where they could carry drugs directly to tumor cells. Existing chemotherapy drugs come with nasty side effects, such as nausea and hair loss, precisely because they can't distinguish different targets.

The nanovalve system might also be adapted to treat degenerative diseases where particular cells are affected, or for the controlled release of insulin to treat diabetes.