Folic Acid Functionalized Zirconium-Based Metal-Organic Frameworks as Drug Carriers for Active Tumor-Targeted Drug Delivery.

Nanoscale metal-organic frameworks (NMOFs) have proven to be a class of promising drug carriers as a result of their high porosity, crystalline nature with definite structure information, and potential for further functionality. However, MOF-based drug carriers with active tumor-targeting function have not been extensively researched until now. Here we show a strategy for constructing active tumor-targeted NMOF drug carriers by anchoring functional folic acid (FA) molecules onto the metal clusters of NMOFs. Two zirconium-based MOFs, MOF-808 and NH2 -UiO-66, were chosen as models to reduce to the nanoscale for application as drug carriers, and then the terminal carboxylates of FA molecules were coordinated to Zr6 clusters on the surfaces of the nanoparticles by substitution of the original formate or terminal -OH ligands. The successful modification with FA was confirmed by solid-state 13 C MAS NMR and UV/Vis spectroscopy and other characterization methods. Drug loading and controlled release behavior at different pH were determined by utilizing the anticancer drug 5-fluorouracil (5-FU) as the model drug. Confocal laser scanning microscopy measurements further demonstrated that 5-FU-loaded FA-NMOFs have excellent targeting ability through the efficient cellular uptake of FA-NMOFs. This work opens up a new avenue to the construction of active tumor-targeted NMOF-based drug carriers with potential for cancer therapies.