Cisplatin-loaded UiO-66-NH2 functionalized with folic acid enhances apoptotic activity and antiproliferative effects in MDA-MB-231 breast and A2780 ovarian cancer cells: An in vitro study

The multifunctional nature of UiO-66-NH₂ as a drug carrier positions it as an optimal candidate for encapsulating and delivering anticancer agents. This study developed a folic acid (FA)-functionalized metal-organic framework (MOF) based on UiO-66-NH₂ to facilitate the targeted delivery of cisplatin (CIS) to MDA-MB-231 breast cancer and A2780 ovarian cancer cells. Fourier transform infrared spectroscopy (FT-IR) confirmed the successful encapsulation of CIS within UiO-66-NH₂, while the drug release profile demonstrated a sustained, pH-responsive release of CIS, with a pronounced increase in the acidic tumor microenvironment. The MTT assay revealed excellent biocompatibility of UiO-66-NH₂-FA with HFF healthy cells, whereas UiO-66-NH₂-CIS-FA significantly enhanced anticancer activity against MDA-MB-231 and A2780 cells. Treatment with UiO-66-NH₂-CIS-FA induced substantial apoptosis in both cell lines, leading to a marked upregulation of <i>BAX</i> and <i>P53</i> gene expression, alongside the downregulation of <i>BCL2, CCND1,</i> and <i>CDK4.</i> Furthermore, cells treated with CIS, UiO-66-NH₂-CIS, and UiO-66-NH₂-CIS-FA exhibited a significant increase in DCF fluorescence compared to the control group, indicating elevated ROS generation. UiO-66-NH₂-CIS-FA demonstrated enhanced drug-loading capacity and cytotoxic efficacy against cancer cells. Functionalization of UiO-66-NH₂-CIS with FA presents a promising strategy for targeted cancer therapy by improving drug delivery specificity and enhancing therapeutic outcomes.