Chitosan Nanoparticles Unlock the Antioxidant Potential of Epigallocatechin Gallate in Pancreatic and Hepatic Cancer Cell Models

Epigallocatechin gallate (EGCG), the predominant catechin in green tea, displays strong antioxidant and cytoprotective properties; however, its poor stability and limited oral bioavailability significantly restrict its therapeutic potential, prompting the need for new therapeutic strategies. Here, we reported synthesis and physicochemical characterization of chitosan nanoparticles (Ch-NPs) encapsulating EGCG (Ch-EGCG-NPs) by the ionic gelation method. The Ch-EGCG-NPs displayed tunable particle size (184–236 nm), narrow polydispersity, and positive zeta potential, supporting colloidal stability and efficient EGCG loading. NPs uptake was followed by confocal microscopy and flow cytometry, using FITC-labeled Ch-NPs demonstrating efficient internalization in pancreatic and hepatic cancer cell models, i.e HepG2 and PANC-1 respectively. In vitro assays revealed that Ch-EGCG-NPs preserved cell viability under hydrogen peroxide–induced oxidative stress and significantly modulated intracellular ROS levels. The oxidative treatment induced a 1.89-fold increase in ROS production compared to the control (corresponding to an 89% up-regulation), representing the largest percentage change observed. Conversely, Ch-EGCG-NPs markedly reduced ROS accumulation compared to free EGCG, lowering ROS levels from 2.24 to 1.06 (≈52.7% reduction) and from 2.24 to 0.66 (≈70.5% reduction), with reductions ranging from 52% to 70.5% in PANC-1 cells and up to 60.3% in HepG2 cells.