Folic acid-conjugated UIO-66-MOF enhances the targeted co-delivery of cisplatin and cyclophosphamide for breast cancer therapy

Breast cancer is the most prevalent cancer among women, accounting for approximately 30% of all cancer cases in the female population. Consequently, the development of effective therapeutic methods for this disease has been a primary focus for researchers. In this study, we present a novel approach involving the co-loading of cisplatin (CIS) and cyclophosphamide (CYP) into a UIO-66 metal-organic framework nanostructure, followed by surface functionalization with folic acid. The anticancer effects of the synthesized nanocarrier (FA-PEG/(CIS+CYP)@UIO-66) were evaluated through in vitro experiments and compared with control samples. The drug content of the FA-PEG/(CIS+CYP)@UIO-66 system was estimated to be approximately 61.92 ± 1.07% for CYP and 74.22 ± 1.25% for CIS. Notably, administration of these nanoparticles resulted in a down-regulation of Bcl2 , MMP-2 , and MMP-9 gene expression, and an up-regulation of Bax , Caspase-3 , and Caspase-9 in the breast cancer cell lines, compared to the control samples (CIS, CYP, and (CIS+CYP)@UIO-66). Additionally, the FA-PEG/(CIS+CYP)@UIO-66 system significantly reduced cell migration and invasion in both SKBR3 and 4T1 cells. Furthermore, the FA-PEG/(CIS+CYP)@UIO-66 system showed effective internalization into SKBR3 and 4T1 cells, with predominant endocytosis due to its selectivity for overexpressed folate receptors in these cell lines. The enhanced uptake, particularly in HER2-positive SKBR3 cells, highlights the potential of these nanoparticles for targeted drug delivery. Overall, the FA-PEG/(CIS+CYP)@UIO-66 therapeutic system demonstrated targeted cancer therapy by combining selective targeting and controlled drug release, thereby increasing apoptosis in cancer cells. • Folic Acid-Conjugated UIO-66 for delivery of Cisplatin and Cyclophosphamide were prepared. • in vitro studies validated the potential of formulations for cancer therapy. • The Folic Acid-Conjugated UIO-66 had a significant effect on inhibiting cancer cell growth.