Targeted pancreatic cancer therapy using 4-farnesyloxycoumarin conjugated nanocrystalline cellulose and Chitosan nanoparticles

This study investigates the effects of 4-farnesyloxycoumarin (4-FOC)-conjugated NCC/CTAB/CS nanoparticles (NPs) on PANC-1 pancreatic cancer cells, highlighting their cytotoxicity and antioxidant properties. Dynamic light scattering (DLS) analysis revealed a Z-average particle size of 275.68 nm, with a polydispersity index of 0.3020. The mean intensity diameter was 334.68 nm, and the mean volume diameter was 380.97 nm. The zeta potential was recorded at 28.88 ± 12.64 mV, confirming good stability due to electrostatic repulsion. Field emission scanning electron microscopy (FESEM) confirmed the successful conjugation of 4-FOC to the NPs, and Fourier-transform infrared (FTIR) spectroscopy validated the incorporation of functional groups. In contrast, the encapsulation efficiency of 4-FOC was measured at 88.49%. Cytotoxicity assays indicated a significant reduction in PANC-1 cell viability, with an IC50 value of 61.23 µg/mL; in contrast, human dermal fibroblast (HDF) cells exhibited greater resilience, maintaining 92.61 ± 2.33% viability at 100 µg/mL. Apoptotic assays revealed a dose-dependent increase in early and late apoptotic cells, with late apoptosis rising to 54.1% at 81 µg/mL. Gene expression analysis showed significant upregulation of caspase 3 (2.25 ± 0.33), p21 (1.70 ± 0.05), and p53 (2.71 ± 0.29 at 61 µg/mL), underscoring the NPs' role in apoptosis and cell cycle regulation. Additionally, the antioxidant capacity of the NPs was confirmed through ABTS and DPPH radical scavenging assays, achieving 38.82% and 68.25% scavenging activity at the highest concentrations, respectively. These findings suggest that 4-FOC-conjugated NCC/CTAB/CS NPs hold promise as a therapeutic strategy for treating pancreatic cancer.