Synergistic anticancer activity of resveratrol-loaded polymeric nanoparticles and sunitinib in colorectal cancer treatment

Abstract

The development of novel and effective treatment strategies, particularly through drug combinations, can significantly enhance therapeutic outcomes. This study explores the innovative combination of resveratrol (RES), a phenolic compound, with sunitinib (SUNI), a multitarget tyrosine kinase inhibitor, for targeting human colon adenocarcinoma cell line HT-29. We identified a synergistic effect at a SUNI:RES ratio of 1:8, based on their half-maximal inhibitory concentration values. Increasing the dosage of the combined treatment led to a notable reduction in cell viability, observed in both two-dimensional (2D) and three-dimensional cell cultures. To improve RES therapeutic efficacy, drug-loaded polymeric nanoparticles (PLGA-RES) were successfully fabricated with an average diameter of 178.4 ± 4.6 nm. The combination of PLGA-RES and free SUNI at the optimal ratio exhibited enhanced anticancer activity, reducing cell viability by approximately 25 and 15% more than PLGA-RES and free SUNI alone, respectively, in 2D cultures. Moreover, this combination therapy demonstrated superior effectiveness in treating HT-29 spheroids over 24 and 48 h. These findings highlight the potential of this combined approach to improve colorectal cancer treatment outcomes. © 2025 The Author(s).