Abstract
This study investigates the characterization and biological effects of Dual Drug-Loaded Nanoparticles on HepG2/doxorubicin (DOX) cells, focusing on the anti-cancer ability of Doxorubicin/Curcumin-Polyethylene Glycol-Polycaprolactone Nanoparticles (DOX/Cur-PEG-PCL-NPs). DOX/Cur-PEG-PCL-NPs, along with single-drug and blank nanoparticles, were prepared and characterized by nanoparticle tracking analysis (NTA) for hydrodynamic diameter and Zeta potential. The morphology of DOX/Cur-PEG-PCL-NPs was characterized by transmission electron microscopy (TEM). Drug loading, encapsulation efficiency, and release profiles were evaluated. In HepG2/DOX cells, the DOX/Cur-NPs significantly reduced viability, migration, and invasion, while promoting apoptosis and reactive oxygen species (ROS) generation. Molecular analyses indicated downregulation of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), NAD(P)H Quinone Dehydrogenase 1 (NQO1), Heme Oxygenase 1 (HO-1), and Multidrug Resistance Protein 1 (MDR1), and upregulation of Kelch-like ECH-associated protein 1 (Keap1), Bcl-2-associated X protein (Bax), and caspase-3. These results demonstrate that DOX/Cur-PEG-PCL-NPs enhance anticancer efficacy by modulating oxidative stress and apoptosis pathways. These results demonstrate that DOX/Cur-PEG-PCL-NPs effectively reverse chemoresistance and suppress tumor progression through modulation of the Nrf2 pathway and apoptosis induction, offering a promising strategy for targeted liver cancer therapy. Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00855-y.