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

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 multi-target tyrosine kinase
inhibitor, for targeting HT-29 colon cancer cells. We identified a
synergistic effect at a SUNI ratio of 1:8, based on their IC50 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 (3D) cell cultures. To improve resveratrol 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 hours. These findings highlight the potential of
this combined approach to improve colorectal cancer treatment outcomes.