|
Researchers in the US have developed a new type of molecular nanovalve that can control the flow of small molecules trapped within porous silica spheres. The device, reported in Angewandte Chemie, could be used as a novel drug-delivery agent as it operates in aqueous conditions and responds to changes in pH. Building molecular machines from the bottom up is one of the aims of nanoscience pioneer Fraser Stoddart and his colleagues at the University of California Los Angeles. Among their many achievements have been shuttle-type molecules that can be moved from station to station using light, electricity and changes in pH. However, until now a molecular valve that would emulate the functionality of a cycle innertube valve or a carburettor has remained elusive at least in one sense. Now, Stoddart and colleagues Jeffrey Zink, Sarah Angelos, Ying-Wei Yang, Kaushik Patel have developed a new type of nanovalve that works in water, rather than an organic solvent. As such, it might one day be developed into a component for a controlled drug-delivery system. By incorporating a nanovalve into a carrier material, such as mesoporous silica, a pharmaceutical could be carried to the target diseased organ, and released under preordained conditions, such as the more alkaline environment of diseased tissue. This would open the valve at the right place and at the right time. To create their nanovalve, the researchers attached stem-shaped bisammonium molecules on to the surface of the porous spheres and filled the pores with guest molecules of fluorescent rhodamine B. Then, at a pH in the range neutral down to acidic values, they skewered pumpkin-shaped cucurbituril molecules on to these "stems". The resulting supramolecular structure, a pseudorotaxane, blocks the pores of the spheres, so that the guest molecules within cannot escape. This is the nanovalve in its closed state. Structural characterisation of the nanoscopic mesoporous silica particles was undertaken using X-ray crystallography and scanning electron microscopy. The researchers found that if they raised the pH to more alkaline levels (pH 10 produced by adding sodium hydroxide solution) this weakens the interaction between the pumpkin-shaped cucurbituril molecules and the stems. The bisammonium stems are deprotonated, the pumpkins are then free to fall off, and the pores they were blocking are opened. With the nanovalves in this state the guest molecules within the porous spheres can readily exit. The team used the emission spectrum of the fluorescent rhodamine B to record the release of the guests in real time at one-second intervals. The researchers concede that the fine details of the individual components need a lot more work before they can be tested as a viable drug-delivery system. "In keeping with the development of prototypical nanovalves, the design of the components usually needs to be optimized to achieve the best possible performance," they say. Indeed, the initial design was quite leaky even at lower, acidic, pH, prior to base activation. They suspected that the pumpkins were simply not sitting quite tightly enough in the openings of the porous channels in the silica nanoparticles when the valves are closed. So, they shortened the stalks on which the pumpkin molecules are skewered. This allowed them to sit further into the pore entrance blocking entirely the escape of the rhodamine B test guest molecules. Another concern was whether or not the silica nanoparticles would degrade at the high pH necessary to open the nanovalves. However, the SEM and XRD data recorded before and after base activation revealed no differences in the pore structure. "No noticeable differences in either the nanoparticle morphology or mesostructure were observed, which indicates that the structure of the nanoparticle supports is preserved during the controlled release process," the researchers say. The ultimate goal is to exploit the very small differences in pH between healthy and diseased tissue so that the change as the nano device moves into its target environment is enough to open the valves without their being able to leak in healthy tissue. Related links:
|
|
