| Summary: | <i>Astragalus</i> alcohol soluble polysaccharide (AASP) could present superior water solubility and antitumor activity with high concentration. Selenium nanoparticles (SeNPs) have received growing attention in various fields, but their unstable property increases the application difficulties. In the present study, functionalized nano-composites (AASP−SeNPs) were synthesized through SeNPs using AASP (average molecular weight of 2.1 × 10<sup>3</sup> Da) as a surface modifier, and the preliminary structural characteristics and inhibitory mechanism on liver cancer (HepG2) cells were investigated. Results showed that AASP−SeNPs prepared under a sodium selenite/AASP mass ratio of 1/20 (<i>w</i>/<i>w</i>) were uniformly spherical with a mean grain size of 49.80 nm and exhibited superior dispersivity and stability in water solution. Moreover, the composites could dose-dependently inhibit HepG2 cell proliferation and induce apoptosis through effectively regulating mitochondria-relevant indicators including Δ<i>Ψm</i> depletion stimulation, intracellular ROS accumulation, Bax/Bcl-2 ratio improvement, and Cytochrome c liberation promotion. These results provide scientific references for future applications in functional food and drug industries.
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