pH-responsive Ni-MOF based nanocarriers with folic acid targeting for enhanced chemotherapeutic efficacy in breast cancer

Abstract

Breast cancer is among the most prevalent malignancies affecting women globally. Conventional chemotherapeutic treatments like 5-fluorouracil (5-FU) are not very effective and can cause serious side effects. To address these challenges, we developed a folic acid-functionalized nickel-based metal–organic framework incorporated with 5-fluorouracil (FA/Ni-MOF/5-FU) as a targeted and pH-responsive nanocarrier for selective breast cancer treatment. The addition of folic acid (FA) made it possible to actively target folate receptors, which are found in high amounts on MDA-MB-231 breast cancer cells. The Ni-MOF acted as biocompatible carrier for controlled drug release. In vitro cytotoxicity assays demonstrated that FA/Ni-MOF/5-FU exhibited superior anticancer efficacy against MDA-MB-231 cells, achieving 83.51% inhibition at 40 µM with IC₅₀ value of 18.5 ± 0.4 µM, compared with free 5-FU (71.23% inhibition, IC₅₀ = 24.4 ± 0.6 µM) and Ni-MOF/5-FU (75.32% inhibition, IC₅₀ = 23.6 ± 0.4 µM). FA/Ni-MOF/5-FU had much less cytotoxicity towards normal MCF-10A breast epithelial cells, keeping 86.54% of them alive (IC₅₀ > 40 µM). Free 5-FU was more toxic (78.43% of them alive, IC₅₀ > 40 µM). The uncoated Ni-MOF had very little effect on both cancer and normal cells (58.91% inhibition on MDA-MB-231 and 13.63% on MCF-10A, IC₅₀ > 40 µM), which shows that it is naturally biocompatible. FA/Ni-MOF/5-FU is a promising nanoplatform for targeted breast cancer chemotherapy. It has better tumor selectivity, folate receptor-mediated uptake, and less systemic toxicity than free 5-FU.