Chondroitin sulfate-decorated cupper-benzene dicarboxylate framework as an efficient passive and active targeting nanomedicine for anticancer methotrexate delivery

In this research, an advanced drug delivery system was developed by decorating the copper-benzene dicarboxylate framework (Cu(BDC)) with the multifunctional chondroitin sulfate (ChS), termed Cu(BDC)/ChS. This novel system is designed for both active and passive targeting, featuring a pH-sensitive release mechanism that enhances drug effectiveness. Different characterization techniques confirmed the successful synthesis of the Cu(BDC)/ChS nanocomposite. In-vitro experiments evaluating the loading and release of methotrexate (MTX) showed that the release rate was significantly higher at pH 4.5, releasing 70 % over 92 h at 41 °C, in contrast to less than 20 % at pH 7.4 at 37 °C. This pH responsiveness of the Cu(BDC)/ChS promotes drug release in environments alike to tumor tissues. Additionally, cytotoxicity tests revealed that MTX-loaded Cu(BDC)/ChS exhibited considerable cytotoxic effects on MCF-7 cancer cells, with IC50 value of ∼250 μg/mL after 48 h, accompanied by an increase in apoptosis rates. Remarkably, the overexpression of CD44 receptors on cancer cell surfaces underscores the significance of ChS-functionalized systems in promoting selective cancer cell apoptosis, while exhibiting minimal cytotoxicity toward normal HUVEC cells. Overall, the findings indicate that the combination of Cu(BDC) and ChS holds promise for developing effective platforms for anticancer drug delivery.