This article introduces an environmentally friendly and more economical method for preparing red selenium nanoparticles (Se-NPs) with high stability, good biocompatibility, and narrow size using yeast as a bio-reducing agent with high antioxidant, immune regulation, and low toxicity than inorganic and organic Se. The yeast-derived Se-NPs were characterized by scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The results revealed spherical-shaped particles of Se-NPs with an average diameter of 71.14 +/- 18.17 nm, an amorphous structure, and surface enhancement with an organic shell layer, that provide precise geometry and stability in the formation of bio-inert gray or black Se-NPs instead of red Se-NPs. Furthermore, the addition of 0.3-0.8 mg/kg Se-NPs in the feed significantly improved the health of mice. As Se-NPs stimulated the oxidative state of mice, it significantly increased the level of GSH-Px, SOD, and AOC, and decreased the level of MDA. The yeast-derived Se-NPs alleviated the immunosuppression induced by cyclophosphamide, whereas protected the liver, spleen, and kidney of mice, stimulated the humoral immune potential of the mice, and significantly increased the levels of I g M, IgA, and I g G. These results indicated that the yeast-derived Se-NPs, as a trace element feed additive, increased the defense of the animal against oxidative stress and infectious diseases and therefore Se-NPs can be used as a potential antibiotic substitute for animal husbandry.
