To investigate the ameliorative effects of selenium nanoparticles (Se NPs) on induced myoblast injury and inhibition of myogenic differentiation.

Using hyaluronic acid (HA) as a stabilizing component，Se NPs were synthesized by reducing sodium selenite with ascorbic acid. The physicochemical properties of Se NPs were characterized by transmission electron microscopy，nanoparticle tracking analysis，Zeta potential measurement，and ultraviolet-visible absorption spectroscopy. The in vitro antioxidant capacity was assessed using the 3，3'，5，5'-tetramethylbenzidine chromogenic system and the 2，2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS^•+) scavenging assay. C2C12 myoblasts were treated with lipopolysaccharide （LPS） to simulate the effects of the inflammatory microenvironment formed by skeletal muscle aging or injury on myoblasts, and a hydrogen peroxide-induced oxidative damage model was also used. The effects of Se NPs on cell viability，apoptosis，reactive oxygen species (ROS)/reduced glutathione (GSH) levels，mitochondrial membrane potential，and the expression of inflammation- and myogenic differentiation-related genes were examined. Myosin heavy chain （MHC） expression，myotube formation，and fusion index were also evaluated.

Se NPs were spherical and well-dispersed，with an average core diameter of （117.96±14.27） nm，an average hydrodynamic diameter of （136.71±18.48） nm，and an average Zeta potential of （-25.99±7.60） mV，showing a characteristic absorption peak at approximately 290 nm. In vitro antioxidant experiments demonstrated that the antioxidant capacity of Se NPs increased with increasing manner. Se NPs exhibited good colloidal stability and cytocompatibility. Treatment with 100-500 ng/mL Se NPs attenuated LPS-induced decreases in cell viability and increases in apoptosis. After Se NPs intervention，LPS-induced ROS accumulation was reduced，GSH levels were increased，the expression of tumor necrosis factor-α, inducible nitric oxide synthase, and interleukin-1β was downregulated，and glutathione peroxidase 1 expression was restored. Concurrently，MHC-positive myotube formation was enhanced，and myotube length，diameter，and fusion index were increased，the expression of muscle atrophy-related genes Atrogin-1 and muscle RING finger protein 1 was downregulated，and the expression of myogenic regulatory factor myogenic differentiation 1 and myogenin was upregulated.

HA-stabilized Se NPs possess favorable antioxidant capacity and can alleviate C2C12 cell injury and improve suppressed myogenic differentiation by mitigating LPS-induced oxidative stress and inflammatory responses.