Abstract

Combination therapy tactics have been considered recently for increasing drug effectiveness and reducing the toxicity of chemotherapy. In this study, a novel core/shell metal-organic framework (MOF) was designed for the co-encapsulation of DOX with a pleiotropic agent like CUR. It is coated with folic acid-activated chitosan and pH-sensitive to enhance treatment efficiency and targeted drug delivery. It was coated with folic acid-activated chitosan and pH-sensitive for targeted delivery. A comparison of the release profiles of curcumin and doxorubicin in all cases shows a stable release and a pH-sensitive behavior during 72 h. The results showed the release rate of curcumin and doxorubicin from FC-MOF compared to the uncoated system at pH = 5 increased by 13 and 9, respectively. We evaluated the efficacy and toxicity of the combined drug delivery system (CUR + DOX) using the MTT test in MCF7 (as a positive folic acid receptor) and HepG2 cells (as a negative folic acid receptor). FC-MOF-DOX at the highest concentrations of 14 and 26 survival was shown in MCF-7 and HepG2 cells, respectively. This increased toxicity confirms that folic acid receptors are involved in more cell uptake. Furthermore, the cytotoxicity results of FC-MOF (CUR + DOX) showed a synergistic effect through the co-delivery of cytotoxic drugs and sensitizing chemical agents. For example, FC-MOF (CUR + DOX) with a molar ratio of (25 CUR + 0.5 DOX g/ml) kills more than 60 of MCF7 cells, whereas MOF-CUR + DOX nanoparticles kill almost 45 of the cells. Hence, with low concentrations of DOX, more antitumor responses are created. Using this targeted drug delivery system, the drug can be delivered to cancer cells in a controlled and targeted way.