Abstract
Triple-negative breast cancer (TNBC), characterized by its aggressive behavior and lack of targeted therapies, remains a major therapeutic challenge. This study presents the synthesis and evaluation of ferulic acid-loaded selenium nanoparticles (FA-SeNPs) coated with alginate (Alg@FA-SeNPs) and chitosan (CS@FA-SeNPs) as potential nanocarriers for TNBC treatment. Ferulic acid was selected for its pro-apoptotic and anti-metastatic properties, despite its limited bioavailability. Encapsulation in SeNPs enhanced its stability and delivery efficiency. Alg@FA-SeNPs exhibited greater cytotoxicity (IC50: 103.6 µg/mL) than CS@FA-SeNPs (IC50: 178 µg/mL) after 48 h. Gene expression analyses showed significant H2AX upregulation with Alg@FA-SeNPs, indicating genotoxic stress, and marked Bcl-2 downregulation with CS@FA-SeNPs, favoring apoptosis. Zeta potential measurements confirmed near-neutral surface charge for Alg@FA-SeNPs and strong positive charge for CS@FA-SeNPs, supporting good colloidal stability. These findings highlight the therapeutic promise of biopolymer-coated SeNPs, particularly alginate-coated formulations, as targeted drug delivery systems for TNBC.