Eventually, the aim of the project is to develop a structure that can pass into cells and respond to the very small differences in pH that occur in diseased and healthy tissues, allowing the release of therapeutically active agents only in diseased cells.
The approach is novel because the nanovalve is capable of functioning in an aqueous environment under physiological conditions, in contrast with older conformations that were only stable while immersed in organic solvents.
The scientists, at the University of California, Los Angeles' NanoSystems institute, modified the surfaces of porous, dye-filled nanospheres creating stem-like structures.
On top of this primary scaffolding the team stacked a series of cucurbit[6]uril units (molecular baskets formed from repeated glycouril that have a characteristic "squashed pumpkin" formation), creating - at neutral to acidic pH - a mechanically-interlocking pseudorotaxane architecture that blocks the nanosphere pores, thereby preventing the release of a test agent, a dye called rhodamine, held within.
However, when the local pH is moved into the basic range, the intramolecular bonds holding the structure in place are weakened, causing the nanosphere pores to open and the dye to be released, while maintaining the structures' overall 2D-hexagonal formation.
The team used luminescence spectroscopy to measure the release of the dye, confirming via absorption analysis that for every 15mg of the particles an average of 3mmol of dye was released.
In effect, the researchers have created a supramolecular conformation that acts as a controllable molcular valve that is stable in an aqueous environment.
The research team, under the leadership of J. Fraser Stoddart and Jeffrey I. Zink, said that although the aqueous-stable nanovalve represents a significant breakthrough in nanomolecular architecture, further work needs to be undertaken to fine tune the process.
Additionally, having proved that differential pH can serve as an appropriate triggering mechanism for drug delivery, the researchers are experimenting with other means of induceing drug release.
Professor Stodart explained that enzyme molecules expressed on the surface of diseased cells could serve this function. He told the MIT's Technology Review that: "if we can play to the presence of an enzyme - specifically in a diseased cell - to break a particular chemical bond, then we can introduce that chemical bond into the machinery."
The technology is described in a paper published in the German journal Angewandte Chemie.
