Dual-ligated Metal Organic Framework as Novel Multifunctional Nanovehicle for Targeted Drug Delivery for Hepatic Cancer Treatment

Abstract In the last decade, nanosized metal organic frameworks (NMOFs) have gained an increasing applicability as multifunctional nanocarriers for drug delivery in cancer therapy. However, only a limited number of platforms have been reported that can serve as an effective targeted drug delivery system (DDSs). Herein, we report rational design and construction of doxorubicin (DOX)-loaded nanoscale Zr (IV)-based NMOF (NH2-UiO-66) decorated with active tumor targeting moieties; folic acid (FA), lactobionic acid (LA), glycyrrhetinic acid (GA), and dual ligands of LA and GA, as efficient multifunctional DDSs for hepatocellular carcinoma (HCC) therapy. The success of modification was exhaustively validated by various structural, thermal and microscopic techniques. Biocompatibility studies indicated the safety of pristine NH2-UiO-66 against HSF cells whereas DOX-loaded dual-ligated NMOF was found to possess superior cytotoxicity against HepG2 cells which was further confirmed by flow cytometry. Moreover, fluorescence microscopy was used for monitoring cellular uptake in comparison to the non-ligated and mono-ligated NMOF. Additionally, the newly developed dual-ligated NMOF depicted a pH-responsiveness towards the DOX release. These findings open new avenues in designing various NMOF-based DDSs that actively target hepatic cancer to achieve precise therapy.