Multifunctional Biogenic Selenium Nanoparticles from Citrus sinensis peel: In Vivo Antioxidant, Antiviral, Antibacterial, Anticancer and Neuroprotective Assessment in Rat Model

Abstract

The development of innovative, multi-targeted therapeutic agents from sustainable sources is essential in veterinary and biomedical sciences. Green synthesis improves the biocompatibility and utility of selenium nanoparticles (SeNPs). This research synthesized selenium nanoparticles using a polyphenolic-rich Citrus sinensis peel extract (Cs-SeNPs) and conducted a comprehensive assessment of their therapeutic efficacy across four principal disease models in Wistar rats. CsSeNPs were synthesized via green reduction using Citrus peel extract, yielding spherical particles 25nm in diameter with a negative zeta potential of-22mV. Selenium nanoparticles showed low cytotoxicity (CC₅₀ >150µg/mL) in TZM-bl and RAW 264.7 cells. They exhibited significant antiviral activity against HIV-1 (IC₅₀ = 58.7µg/mL) and the murine norovirus surrogate MNV-1 (IC₅₀ = 41.2µg/mL). Therapeutic efficacy was evaluated in 250 rats across models of CCl4-induced oxidative stress, Staphylococcus aureus and Escherichia coli-infected wounds, DMH-induced colon cancer, and ICV-STZ-induced Alzheimer’s disease. CsSeNPs significantly (P<0.001) restored endogenous antioxidant status and reduced lipid peroxidation by 75%. In the wound model, topical Cs-SeNPs achieved 99% wound closure and a 95% decrease in bacterial load within 14 days. Anticancer activity was robust, reducing tumor burden by 70% and inducing apoptosis, as evidenced by a 5-fold increase in the Bax/Bcl-2 ratio. In the neurodegeneration model, Cs-SeNPs significantly enhanced cognitive performance, reduced AChE activity by 45%, and decreased amyloid-beta plaque load by 60%. In conclusion, biogenic Cs-SeNPs constitute a highly efficient, single therapeutic agent exhibiting robust in vivo antioxidant, antimicrobial, anticancer, and anti-Alzheimer’s efficacy.