Co-delivery of doxorubicin and curcumin to breast cancer cells by a targeted delivery system based on Ni/Ta core-shell metal-organic framework coated with folic acid-activated chitosan nanoparticles

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.