The biological activity of amorphous selenium nanoparticles (SeNPs) was limited by their poor stability and rapid spontaneous phase transformation. Herein, we prepared amorphous SeNPs by decorating them with lichenan (LC), a natural random coil conformation polysaccharide, through C–O⋯Se bonds or O–H⋯Se bonds. The synthesized amorphous spherical LC-SeNPs maintained their amorphous phase and zero valence state after being stored for 60 days at 4 °C. This stability can be also maintained under different heating treatment temperatures (37, 55, 75, and 95 °C), pH conditions (pH 3–10), and ionic strength (10–200 mM). Furthermore, LC-SeNPs displayed potential anticancer efficacy based on their ROS-triggered selenium release property and variable redox potential in the ROS model. The underlying antiproliferative mechanism was related to cell cycle arrest, intracellular redox imbalance, and mitochondrial dysfunction. This work provides a promising strategy for using LC-SeNPs in diet supplements or cancer chemoprevention.
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