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Selenium nanoparticles (SeNPs) produced via bio-mediated (green) routes are attracting interest for antimicrobial, antiviral, anticancer, antioxidant, anti-inflammatory, and antidiabetic applications. SeNPs remain a very significant entity in nanobiotechnology. Green chemistry, which involves synthesizing nanoparticles (NPs) using biological materials such as plants, microorganisms, and fungi, is considered safe and offers significant advantages over other approaches. This review critically examines bacterial, fungal, and plant synthesis mechanisms, tunable parameters (pH, temperature, precursor, reaction time), and required physicochemical characterization (size, PDI, ζ-potential, crystallinity, surface chemistry). The synthesis evidence from in vitro and in vivo studies highlights variability introduced by capping chemistries and identifies common assay interferences and safety gaps (dose normalization to elemental Se, protein corona, biodistribution, immunotoxicity). Finally, we outline design rules and translational considerations (stability, sterilization, scalability) to guide the development of reproducible, biocompatible SeNPs. Notably, green chemistry for the synthesis of SeNPs has been experimentally demonstrated as a promising approach for addressing health challenges across antimicrobial, antioxidant, antidiabetic, anticancer, and anti-inflammatory activities through multifaceted mechanistic pathways. However, these are greatly influenced by the capping agents and their phytochemical compositions. Despite considerable promise, some limitations have been identified: methodological variation encompassing the green-mediated synthesis conditions, a larger percentage of studies are mostly in vitro assays, and a lack of standardized physicochemical characterization across different studies. Hence, successful translation will depend on future prioritization of optimization of existing methods, with sufficient clinical studies ( in vivo ) executed, coupled with in-depth studies to understand their mechanism of action, and comprehensive toxicity.
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Abel et al. (2026) studied this question.
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