**1. Introduction**

Selenium is an essential micronutrient for humans and animals [1]. It is an integral component of more than 30 kinds of selenoproteins and selenium-containing enzymes, such as selenoprotein P (SelP), selenoprotein S (SelS), selenoprotein M (SelM), subfamilies of thioredoxin reductases (TrxR), glutathione peroxidases (GPx), and iodothyronine deiodinases (ID), that play a key role in regulating redox balance and preventing cellular damage from radicals [2,3]. However, at least one billion people in the world are at risk of selenium deficiency at present because the intake of selenium is insufficient to meet the daily requirement [4]. Epidemiological studies established that selenium deficiency is associated with many diseases, including premature aging, a decline in sperm motility, myocardial failure, neurological diseases, endemic osteoarthropathy (Keshan disease), and ischemic heart disease [5]. Although high-dose sodium selenite, methyl selenium, and selenocysteine exhibit excellent bioactivities, they can also result in serious toxicity problems, leading to many diseases [6]. Thus, it is of great importance to seek novel selenium species as food supplements or additives.

**Citation:** Chen, W.; Cheng, H.; Xia, W. Construction of *Polygonatum sibiricum* Polysaccharide Functionalized Selenium Nanoparticles for the Enhancement of Stability and Antioxidant Activity. *Antioxidants* **2022**, *11*, 240. https:// doi.org/10.3390/antiox11020240

Academic Editor: Stanley Omaye

Received: 20 December 2021 Accepted: 26 January 2022 Published: 26 January 2022

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Selenium nanoparticles (SeNPs) have gained much attention owing to their unique physical, chemical, and antioxidant activities [7]. Moreover, SeNPs have higher bioavailability and lower toxicity in comparison to other chemical forms of selenium, making them the promising alternative selenium source in food dietary [8]. However, SeNPs alone with valence state zero are highly unstable in an aqueous solution and easily transform to aggregate, resulting in lower bioactivity and further limiting their practical application [9]. Many efforts have been made to develop a simple, efficient, and green strategy for the dispersion and stabilization of SeNPs using bioactive templates [10]. Natural polysaccharides not only have complex structures, large specific surface areas, and ionizable functional groups but also possess excellent biocompatibility and biodegradability [11]. These features could decrease the surface energy of SeNPs, further preventing aggregation through electrostatic interaction or hydrogen bonds. Thus, polysaccharides applied as carriers to fabricate SeNPs with desired characteristics, such as stability and functionality, using the green chemical method is drawing much attention recently. For example, numerous studies reported that chitosan (CS) could be used as templates to prepare uniform SeNPs and the ligated SeNPs remain stable for over 1 month [12]. However, the superior properties of CS are limited due to its water insolubility and our previous research also found that CS-SeNPs aggregated under alkaline conditions (pH ≥ 9) [13]. Several polysaccharides derived from fungi [14], fruit [15], and medicinal plants [16] have been demonstrated to enhance the antioxidant activity of SeNPs. Recently, medicinal plant polysaccharides have attracted increasing attention due to their significant bioactivities with no side effects [17]. Therefore, it can be expected that the combination of medicinal plant polysaccharides with SeNPs will reduce the inherent limitations and enhance the benefits of selenium and polysaccharides.

*Polygonatum sibiricum* is a traditional Chinese herbal medicine, belonging to the *Liliaceae* family, which has been introduced in the 2015 edition of pharmacopeia [18]. China has abundant resources of *Polygonatum sibiricum*, especially in the south of the Yangtze River [19]. The constituents of *P. sibiricum* include polysaccharides, saponins, flavonoids, alkaloids, lignin, vitamins, and a variety of trace elements, of which polysaccharides are the major pharmacologically active ingredients [20]. In the last three years, *Polygonatum sibiricum* polysaccharides (PSP) are demonstrated to exhibit a wide range of pharmacological activity [21], such as osteogenic activity [22], anti-diabetes [23], immunological activity [24], and especially antioxidant activity, which makes them suitable for application in functional foods and therapeutic agents. PSP demonstrated strong antioxidant properties, which could attenuate D-gal-induced heart aging [25] and protect the mice livers against ethanolinduced oxidative damage via inhibiting oxidative stress [26]. However, no study has been reported using PSP as a decorator to functionalize SeNPs.

In this study, considering the antioxidant activity of PSP as well as the drawbacks of SeNPs, a combined strategy was conducted to fabricate SeNPs using PSP as a stabilizer in the redox system of sodium selenite (Na2SeO3) and ascorbic acid (Vc) through a simple chemistry approach. The synthesized PSP functionalized SeNPs (PSP-SeNPs) were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), energy dispersive X-ray (EDX), ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FTIR), and X-ray photoelectron spectrometer (XPS). The physicochemical stabilities of synthesized nanoparticles under varying conditions, including ionic strength, pH, and temperature, were analyzed. In addition, the antioxidant activity of PSP and PSP-SeNPs was quantified by ABTS and DDPH free radical scavenging assays. Moreover, the protective effect on the H2O2-induced cell death was also investigated by MTT assay.
