Green-synthesized rhein-selenium nanoparticles exhibit potent and highly selective anticancer activity against colon cancer via apoptosis and gene regulation

Rh-Se-NPs exhibited spherical morphology (32 ± 5 nm, TEM), a hydrodynamic diameter of 90.4 nm (DLS), and high colloidal stability (zeta potential: 31.1 mV). Compared to free Rhein, Rh-Se-NPs demonstrated significantly enhanced cytotoxicity, reducing IC50 values by more than two-fold and increasing selectivity indices to 12.85 (DLD-1) and 6.93 (SW620). Functional assays confirmed inhibition of cell proliferation and migration. Apoptosis was evidenced by elevated caspase-9 and caspase-3 activities. Gene expression analysis revealed strong downregulation of oncogenes (CEA, FOXQ1, CXCL17, VEGFA) and marked upregulation of the tumor suppressor PTEN (up to 15.9-fold). This study demonstrates, for the first time, that Rh-Se-NPs act as a biocompatible phytochemical-selenium nanoplatform with dual anticancer mechanisms: apoptosis induction and oncogene suppression. The findings highlight Rh-Se-NPs as a promising, sustainable, and highly selective therapeutic strategy for colon cancer.