Nanotherapeutics have the potential to be more effective and less harmful than traditional medicines, as exemplified by those that are successful. However, most diseases are more complex than the nanotherapeutics that have been developed. The best model for an efficient drug delivery system is viruses, which have functionality on their outer surfaces to avoid detection by the immune system, as well as switchable targeting components that direct them to specific cells. On the interior, viruses have multiple additional components that work in combination to take over the cell. For a nanotherapeutic to mimic these viral strategies, the drug delivery system must be multicomponent and well-defined, i.e., the exact structure and ratio of components must be known. Nanocrystalline, porous, uniformly multifunctionalizable metal-organic framework (MOF) materials fit these criteria. MOF materials are synthesized by the assembly of metal cation clusters and organic linker molecules, and the structure and chemical environment of the pores is extremely tunable. KSU-1, a MOF previously reported in our lab, has amines and hydroxyls as independently reactive functionalities so that functionalization is performed uniformly, rather than randomly. In addition to this uniform multifunctionalization strategy, a surface selective modification methodology based on hydrophobicity can be employed so that the external and internal surfaces of MOF nanocrystals can each be functionalized separately, for a total of four distinct components. The goal of this project is two-fold: I) uniform external functionalization of MOF nanocrystals with a component for stealth and a component for active targeting, designed for stimuli-responsive targeting, and II) uniform internal functionalization with two drugs in known ratios, which will be attached with linkages that are responsive to multiple stimuli for release of the drugs. The progress of this project will be presented.

Metal-organic framework (MOF) materials as scaffolds for multifunctional drug delivery systems

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