Therapeutic effects of dual-ligated doxorubicin-loaded nanosized metal organic framework decorated with obeticholic acid as a novel nuclear targeting of hepatocellular carcinoma

In this work, we developed a novel and successful hepatocellular carcinoma (HCC) therapeutic approach by constructing doxorubicin (DOX)-loaded biocompatible NH2-UiO-66 NMOF decorated with cellular and nuclear targeting ligands. The design, synthesis and biological evaluations of the NMOF covalently ligated with obeticholic acid (OCA) and lactobionic acid (LA) and loaded with DOX were performed and proved efficient HCCtargeting at both the cellular and nuclear levels and simultaneously for active drug delivery. OCA was exploited as a nuclear targeting agent with affinity towards FXR receptor and also as an anticancer drug that is effective against HCC. NMOF was synthesized and covalently decorated with LA or OCA either alone or as dual-ligated. Comprehensive characterization techniques including XRD, FTIR, DSC and BET were used to demonstrate the success of the ligation procedure. The pristine NMOF, mono-ligated and the dual-ligated NMOFs were loaded with DOX and the cell viability was performed on HepG2 cell line as a representative for HCC. The in -vitro experiments confirmed that the drug -free NMOF was safe and biocompatible for normal cell lines such as human skin fibroblast (HSF). However, compared with either non-ligated or mono-ligated DOX-loaded nanoformulations, the DOX-loaded dual-ligated NMOF affirmed a distinguished activity against HCC. These outputs indicate that the developed DOX@OCA-LA-NMOF nanoformulation has superior killing effects on hepatic tumors because of the concentrated drugs localized in tumor cells and the precise targeting affinity of HepG2 cells.