Drug Delivery Project

The overarching goal of this project is to improve the tunability of mesoporous silica drug delivery vehicles, which can encase cancer therapeutics. Such delivery vehicles offer the potential to administer drugs only at the tumor site of the afflicted patient, thus minimizing the exposure of these drugs to healthy tissue and reducing their harmful side-effects.

 

In order to achieve high-selectivity, however, it will be necessary to manipulate the surface properties of the delivery vehicles, and to be able to do so using mild and efficient chemistry. To this end, we have set out to build a new, highly versatile mesoporous silica nanoparticle (MSNP), which is decorated with oxyamine functional groups. This particular brand of functional group is well known to react with carbonyl groups under mild conditions, to form oxime ethers, which are stable for days in a physiological setting. Besides the high-yielding and mild nature of this ligation reaction, it also takes advantage of extremely convenient coupling partners – namely, aldehydes or ketones. The rapid preparation of libraries of uniformly functionalized MSNPs would be a timely boon as this targeted delivery technology reaching the stage of development whereupon extensive screening and iterative improvements will have to be made to optimize the nanoparticles’ properties in preparation for their application in a clinical setting. Opportunities to ligate large biomolecules to the exterior of MSNPs will also be opened up, which would have implications for advanced hybrid inorganicbiological delivery systems. Another facet of the oxime ether linkage proposed here is its reversible nature. This dynamic chemistry also offers exciting possibilities in the realm of mixedmonolayer nanoparticles, which are of considerable current interest.

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