Poly(vinylidene fluoride) Membranes for Synergistic Multidrug Delivery in Resistant Breast Cancer

One of the main challenges in treating cancer is multidrug resistance (MDR), which can result in therapy failure and tumor recurrence. Therapies like chemotherapy, radiation, hormonal therapy, and immunotherapy are being employed to treat cancer and its recurrence. However, all of these methods have significant limitations, including their inability to control micrometastasis, cancer stem cell proliferation, and the development of multidrug resistance during follow-up treatments. Herein, we developed a multidrug-loaded poly(vinylidene fluoride) (PVDF) membrane with a combination of anticancer drugs like cisplatin (Cis), 5-fluorouracil (5-Fu), and doxorubicin (Dox) (MDP), and their anticancer efficacy was tested against MDR cancer cells. We observed that the MDP membrane is biocompatible and showed sustained drug release for more than 72 h. The MDP membrane showed a 2-fold reduction in IC50 concentration compared to free drugs in metastatic breast cancer cell lines (MDA-MB-231). Further, fluorescence-activated cell sorting (FACS) results confirmed that MDP induced late apoptosis in nearly 66.61% of cells and necrosis in the remaining cells. Also, we performed an ex-ovo chick chorioallantoic membrane tumor angiogenic (CAM) assay, and the results showed that the MDP membrane exhibited antiangiogenic properties in the tumor microenvironment, thus controlling metastasis by downregulating angiogenic marker genes, including vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2), and angiopoietin 1 (ANG1). These findings suggest that the MDP could be a promising implantable membrane for preventing postoperative cancer recurrence by delivering a multidrug.