**Table 4.** *Cont.*


**Table4.***Cont.*

↑ higher level; ↓ lower level; G+ gram-positive bacteria; G- gram-negative bacteria.

The strengths, weaknesses, opportunities, and threats (SWOT) analysis for a brief overview of advances and weaknesses of SeNP application in animal nutrition is proposed in Figure 1.

**Figure 1.** The strengths, weaknesses, opportunities, and threats (SWOT) analysis of SeNP application in animal nutrition.

#### *4.3. Synthesis by Plants and Microorganisms*

Live plants; plant tissues; and extracts from the plant leaf, latex, root, seed, and stem, or the whole plant have also been used to synthesize NPs, as they act as stabilizing or reducing agents [189,190]. Due to their genetic variability, plants possess many interesting metabolites, such as phenolic compounds, alkaloids, and sterols, that can serve as excellent biocapping and/or reducing agents. In NPs biosynthesis, plant polyphenols, which possess hydroxyl reducing groups, are usually used as stabilizing and reducing agents. Hydroxyl groups of biologically active plant compounds can also act as a capping agen<sup>t</sup> by depositing on the NPs' surfaces. Polyphenols and proteins may play a key role in reducing selenium ions to their element and stabilizing the SeNPs' form [191]. Polysaccharides may effectively improve the NPs' stability and morphology [192]. The different preparation methods of the plant extract from the same plant tissue may also significantly affect the shape, size, and distribution of NPs [193].

Singh et al. [193] used different *Zingiber officinale* rhizome extract preparation methods and obtained NPs with different properties. The significant advantage of plant-mediated NP synthesis is the inexpensiveness of culture compared to synthesis using microorganisms. In addition, it reduces the cost of microorganism isolation and further NP purification [194]. Moreover, plant-mediated NPs are stable, reproducible, environmentally friendly, and less time-consuming to produce [195]. Anu et al. [167] used *Allium sativum*

extract to produce SeNPs and synthesized NPs 40–100 nm in size, showing decreased cytotoxicity compared to chemically produced SeNPs. SeNPs mediated from various plant extracts (e.g., *Diospyros Montana*, *Murraya koenigii, Ephedra aphylla,* and *Thymus vulgaris*) were reported to have antifungal, anticancer, and antimicrobial activity [108,168,196,197]. Green synthesis of SeNPs is commonly achieved by reducing selenate/selenite in the presence of bacterial proteins and plant extracts containing various metabolites such as phenols, flavonoids, alcohols, and proteins. Many microorganisms (e.g., *Herbaspirillum* sp., *Bacillus arseniciselenatis*, *B. selenitireducens*, and Comamonas testosteroni) have been observed to reduce toxic selenate and selenite into the nontoxic element selenium through aerobic or anaerobic conditions [189,198,199]. Microbes can produce NPs either intra- or extracellularly via different bioreduction processes using various microbial enzymes [190]. Microbial NP synthesis includes two reduction processes (reduction from selenate to selenium trioxide and then to elemental selenium), catalyzed by selenite and selenate reductases [200].

The study conducted by El-Saadony et al. [201] showed that SeNPs synthesized using *Lactobacillus paracasei* had an antagonistic effect against pathogenic fungi and significantly inhibited the growth of *Candida* and *Fusarium* species, which are the most known animal pathogenic species. Moreover, the diameter of obtained SeNPs ranges from 30 to 50 nm. In comparison, a previous study by Sasidharan and Balakrishnaraja [202] synthesized SeNPs by bacteria species (*Lactobacillus casei; Streptococcus thermophilus; Bifidobacterium; Lactobacillus acidophilus; Lactobacillus helveticus; Klebsiella pneumoniae*), but the disadvantage was the size of the produced NPs ranged from 50 to 550 nm. SeNPs synthesized using various cyanobacteria extracts (e.g., *Nostoc sphericum*, *N. punctiforne*, *Spirulina pratensis,* and *Athrospira indica*) showed good antioxidant activities and are recommended for future use as food supplements [203].

SeNPs can play an important role in eliminating microbial infections and, thus, improving animals' growth and performance. SeNPs can inhibit both Gram-negative and Gram-positive bacteria by interrupting microbial biofilm [204] and possess significant antifungal activity by inhibiting spore germination [153]. The antifungal activity of SeNPs was tested mostly by in vitro experiments, and more extensive research in this field is needed. Shakibaie et al. [106] demonstrated a good potential of using bacteria *Bacillus* sp. for SeNPs synthesis. SeNPs prepared using these bacteria were orally administered to male mice, and biogenic SeNPs showed significantly less toxicity than synthetic SeNPs and SeO2.

Nevertheless, the reason for such a difference is not clear. Some in vivo experiments with biogenic SeNP dietary inclusion showed an improved oxidative status in tested animals without toxic effects [125,153,154]. Shirsat et al. [205] demonstrated a protective effect against the oxidative and immune stress of biogenic SeNPs synthesized using the bacteria *Pantoea agglomerans* in broilers' diets. Song et al. obtained promising results, which used yeas<sup>t</sup> *Kluyveromyces lactis GG799* for SeNPs production. SeNPs demonstrated no toxicity in mice. Moreover, dietary supplementation with 0.6 mg/kg Se effectively attenuated oxidative stress, intestinal inflammation, and intestinal barrier dysfunction. However, these experiments are only a few, and further investigation of the impact of biogenic NPs on animals' performance and production is required.

#### *4.4. Synthesis of SeNPs by Marine Algae and Microalgae*

Marine algae generally contain a wide spectrum of biologically active compounds such as polysaccharides, proteins, PUFA, various pigments, and antioxidants. Considering this spectrum, it predestines them to diverse commercial applications [206]. Marine algae may represent a novel nanotechnological solution that could facilitate the application of new alga-mediated NPs in medicine and animal nutrition. Some algae (e.g., *Chlorella vulgaris, Sargassum wightii, Spirogyra insignis, Chondrus crispus, and Tetraselmis kochinensis*) were used for the synthesis of metallic NPs such as Ag and Au NPs [207–210]. SeNPs synthesized via *Spirulina pratensis* showed antibacterial activity against foodborne microorganisms

(*Staphylococcus aureus* and *Salmonella typhimurium*), but antibacterial activity increased with NP size reduction [211]. Aqueous extract of algae *Sargassum angustifolium* was used for biosynthesis of SeNPs, which were finally examined on antibacterial activity. Algae-coated SeNPs showed better antibacterial activity against *Vibrio harveyi* compared to uncoated SeNPs [212]. Algal cell walls are mainly composed of polysaccharides, natural polymers containing monosaccharides linked with glycosidic bonds. In recent years, the application of diverse algal polysaccharides (e.g., alginate and laminarin) has been reported [213]. Developing drug delivery systems using seaweed polysaccharides has received special attention in the scientific community due to the important field of biomedical research. Algal polysaccharides were successfully used for coating NPs as a stabilizing agent. The hydrophilic surface of functional groups on polysaccharides (e.g., hydroxyl, sulfate, and carboxyl groups) allows them to easily interact with biological tissues. Therefore, algal polysaccharides can serve as an excellent template for NP synthesis in modern nanotechnology.

Colloidal stability is frequently an issue that requires significant consideration since high agglomeration levels have been recorded in some situations [214]. The use of algae in NP production is also limited due to the lack of understanding of the synthesis mechanism. Studies regarding the employment of marine algae for SeNP production are still ongoing. It is believed to have a wide potential in the synthesis of biogenic NPs with interesting new properties.
