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

Graphical Targeted drug delivery : Nanoscale metal–organic frameworks modified with folic acid (FA-NMOFs) have been prepared as potential drug carriers for targeted delivery to tumor cells (see figure). The anticancer drug 5-fluorouracil (5-FU) was encapsulated in the pores of the FA-NMOFs. The 5-FU-loaded FA-NMOFs showed excellent biocompatibility and were found to effectively kill tumor cells through the targeting effect of the FA-NMOFs. 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 NH 2 -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 Zr 6 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.