Revolutionizing fisetin's anticancer potential: nanotechnology and computational approaches unveil enhanced CT-DNA interactions and bioavailability of nano-fisetin

Abstract

Fisetin (FIS), a natural flavonoid, exhibits notable anticancer properties but suffers from poor bioavailability. This study investigates the enhanced interaction of nanotized fisetin (Nano-FIS) with calf thymus DNA (CT-DNA) and its superior anticancer efficacy toward the SW480 cancer cell line. Comprehensive characterization of FIS and Nano-FIS interactions with CT-DNA was performed via a series of spectroscopic as well as computational studies. We explored the structural alteration induced by biocompatible Nano-FIS in CT-DNA for the first time. This novel finding could be an effective approach to control cancer cells at the gene level. Computational studies, including molecular docking, density functional theory (DFT) calculations, molecular electrostatic potential (MESP) analysis, pharmacophore modeling, and ADMET profiling, provided detailed insights into the binding mechanisms and predicted improved bioavailability and therapeutic potential of Nano-FIS. Our results demonstrated that Nano-FIS forms more stable complexes with CT-DNA, resulting in a significantly lower IC50 value of 50 μM mL⁻¹ in SW480 cells compared to 120 μM mL⁻¹ for FIS, thereby showcasing its potential as an effective anticancer agent.