Enhanced apoptotic effects of nano-encapsulated curcumin and capsacin: synthesis, characterization and anticancer activity in HepG2, MCF7, and A549 cells

Abstract Curcumin and capsaicin are natural compounds with known therapeutic potential but limited clinical utility due to poor solubility and bioavailability. In this study, nanoformulations of curcumin and capsaicin were developed using the thin-film hydration method and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The nanocapsules demonstrated enhanced physicochemical stability, with capsaicin nanoparticles averaging ~ 49 nm and curcumin ~ 76 nm. Cytotoxicity assays in HepG2 (Human hepatocellular carcinoma (liver cancer)), MCF-7 (Human breast adenocarcinoma), and A549 (Human lung adenocarcinoma epithelial) cell lines revealed potent anti-proliferative effects, especially when both nanoparticles were combined, indicating a synergistic interaction. Gene expression analysis showed upregulation of pro-apoptotic markers ( p53 and Bax ) and downregulation of anti-apoptotic Bcl-2 , confirming apoptosis induction via the p53/BAX/BCL2 pathway. These findings highlight the potential of nano-curcumin and nano-capsaicin as effective, complementary anticancer agents and support their further development for biomedical applications.