A multivariate metal-organic framework based pH-responsive dual-drug delivery system for chemotherapy and chemodynamic therapy

Combination therapy has emerged as a promising strategy due to its synergistic therapeutic pathways that enhance anticancer efficacy and limit the emergence of drug resistance. In this work, MIL-88B type multivariate (MTV-1) nanocarriers based on a mixed linker (1,4-benzenedicarboxylic acid and biphenyl-4,4 '-dicarboxylic acid) and metals (iron and cobalt) were synthesized. The presence of the distinct linkers modified the pore makeup of MTV-1 and facilitated the co-encapsulation of two anticancer drugs of varying molecular sizes: 5-fluorouracil (5-FU) and curcumin (CUR). The drug loading measurements on MTV-1@5-FU + CUR represented a loading capacity of 15.9 wt% for 5-FU and 9.3 wt% for CUR, respectively. They further exhibited a pH-responsive drug release pattern with higher concentrations of 5-FU and CUR released at pH 5.5 (simulating cancer microenvironment) compared to pH 7.4 (physiological environment). Moreover, we also demonstrated that MTV-1 MOFs, due to the presence of mixed valence metal ions, could exhibit peroxidase-like activity and catalyze H2O2 decomposition to produce OH radicals for chemodynamic therapy. Cell cytotoxicity assays exhibited significant inhibitory effects of MTV-1@5-Fu + CUR against HepG2 cells with an IC50 of 78.7 mu g mL-1. With dual-drug loading, pH-responsive release, and chemodynamic therapy, MTV-1 shows excellent potential for multifunctional anticancer treatment. By combining two different ligands and metals, MOFs can be fine-tuned for effective encapsulation and delivery of two anticancer drugs.