Nonsuwan P.Niwetbowornchai N.Insawang K.Kunwong N.Srichan K.Srisawat C.Dana P.Saengkrit N.Nguyen K.T.Punnakitikashem P.Mahidol University2025-05-092025-05-092025-04-23Royal Society Open Science Vol.12 No.4 (2025)https://repository.li.mahidol.ac.th/handle/20.500.14594/109977The 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.MultidisciplinaryArticleSCOPUS10.1098/rsos.2418172-s2.0-10500365258320545703