Selective cytotoxicity of Ferulic Acid-Loaded ZIF-8 nanoparticles and free Ferulic Acid on ovarian carcinoma and dental pulp stem cells

Purpose: To overcome the rapid oxidation and low stability of Ferulic Acid (FA), this study designed and characterized FA-loaded Zeolitic imidazol framework -8 (FA-ZIF-8) nanoparticles, evaluating their selective cytotoxic, anti-proliferative, anti-migratory, and apoptotic effects on OVCAR-3 and SKOV-3 ovarian cancer cells alongside healthy primary dental pulp stem cells (DPSCs).Materials and methods: FA-ZIF-8 nanoparticles were synthesized and characterized. OVCAR-3, SKOV-3, and DPSC cohorts were treated with varying concentrations of FA (5 μM–1 mM) and FA-ZIF-8 (25–500 μg/mL) for up to 72 h. Cell viability and 48-h half-maximal inhibitory concentrations IC50 were quantified using the XTT assay. Transcriptional and translational expressions of apoptotic markers were analyzed via qRT-PCR and immunocytochemistry and TUNEL analysis. Long-term survival and lateral cell motility were monitored via coloni and scratch wound healing assays.Results: FA exhibited a non-toxic profile, actively stimulating the proliferation of both cancer lines and DPSCs. FA-ZIF-8 inverted this response, yielding 48-h IC50 values of 308.2098 μg/mL for OVCAR-3 and 336.3022 μg/mL for SKOV-3. FA-ZIF-8 upregulated Bax expression and Caspase-3 levels while suppressing Bcl-2, driving a significant increase in the Bax/Bcl-2 (p=0.0024). These results were confirmed by an increase in TUNEL-positive apoptotic cell. Furthermore, FA-ZIF-8 inhibited colony formation and significantly reduced lateral migration indices, particularly in SKOV-3 lines.Conclusion: FA acts as a proliferative ligand, its strategic formulation into FA-ZIF-8 nanoparticles enables a, "Trojan Horse" effect, delivering selective cytotoxicity, anti-metastatic suppression, pH-responsive apoptotic induction to epithelial ovarian cancer cells.