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A new nanovalve that opens in response to pH changes could serve as the basis of a targeted drug delivery system. By filling a tiny, porous silica sphere with a drug and then plugging the pores with the valves, researchers can use pH changes to control the drug’s release.

The pH of healthy and diseased tissues often differs, meaning the spheres could be designed to release the drug in diseased tissue only, says J. Fraser Stoddart, professor of chemistry at Northwestern University. Stoddart, along with UCLA chemistry professor Jeffrey Zink, led the development of the new nanovalve; their findings were announced in last week’s issue of the journal Angewandte Chemie.

Previous versions of the valve functioned only in organic solvents and were activated by elaborate oxidation reactions. By switching to a pH-activated mechanism, the researchers made the valve functional in water–a critical feature for any drug delivery system. “We’re now putting a lot of emphasis on systems that are biocompatible,” says Stoddart.

Other pH-sensitive nanovalves have been proposed, but “a lot of things we’ve worked on in the past are theoretical and can’t be made yet,” says Santiago Solares, an assistant professor of mechanical engineering at the University of Maryland who was not involved with the work. The new valve, on the other hand, has already been prototyped and tested for use in water.

The core of the system is a rigid silica nanosphere riddled with a honeycomb-like network of pores, which are filled with “guest molecules” that will be selectively released. In their test of the valves, the researchers used a dye called rhodamine as the guest molecule. If the system were used for drug delivery, the guest molecule would be the drug.

In addition to the guest molecules, a skewerlike molecular stalk is inserted into each pore. The stalk protrudes from the sphere’s surface, impaling a donut-shaped molecule called cucurbituril, which effectively plugs the pore and prevents the guest molecules from leaking out.

At just 400 nanometers in diameter, says Stoddart, the tiny spheres would easily be taken up by cells. Once inside, they would respond to the cells’ internal pH and either retain or release their contents.

At neutral to acidic pH, the cucurbituril is bound to the stalk by electrostatic forces, and the plug remains in place. But when the pH turns basic, these forces are disrupted, and the “donut” falls completely off its “skewer.” With the cucurbituril plug gone, the guest molecule–be it dye or drug–is free to leak out of the silica sphere’s pores.

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Credit: Kaushik Patel and Hussam Khatib

Tagged: Biomedicine, nanomedicine

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