Design of Highly Porous MOFs for Drug Delivery

Metal-organic frameworks (MOFs) are ideal candidates for payload delivery in drug delivery applications due to their highly tuneable surface properties, with drug capacities as high as 60 wt.%. The use of MOFs can lower the required amount of active pharmaceutical ingredient (API), providing a more efficacious therapy while also decreasing the potential for untargeted and undesired effects. Their controlled and autonomous delivery utilizing such a porous high-capacity loading material ultimately could reduce high dependence on patient compliance.<br/><br/>We have developed a series of nano-sized Zr-MOFs with different pore sizes and volumes, from the microporous UiO-66 family of materials to mesoporous NU-1000, all of them showing minimal cytotoxicity. On the one hand, we show how the post-synthetic modification of the MOFs can allow the controlled release of different payloads, extending the release time from 2 days to 30 days. On the other hand, we show how the particle size and surface chemistry allow tuning the final fate of the MOFs and the metabolic pathways of how they are endocytosed by the cells. By modifying the external surface chemistry of the MOFs or by grafting different motifs, we can extend the release time of the drugs, and improve the efficiency of the MOFs to penetrate the cells and target specific organelles.<br/><br/>Our work has allowed us to understand the fundamental biophysical and biochemical mechanisms of cancer cell death upon treatment with MOFs. The fundamental understanding of the biological aspects of cancer has allowed us to advance not only in small-drug molecule delivery but also in novel solutions based on photodynamic therapy and gene therapy.