Possible application of nano-selenium and the associated safety in the veterinary field: a summary overview

Review methodology

Various databases have been used to collect original articles on selenium nanoparticle synthesis, biomedical applications, and experimental studies using different animal models. The antioxidant properties, safety, and possible toxicities were also considered. Databases included the Web of Science, PubMed, Academia, and Google Scholar. The review includes research results from more than three decades.

Introduction

Selenium (Se) is a crucial element in nature. Its deficiency can lead to cardiovascular disorders, liver dysfunction, weakened immunity, and diseases such as Kashin–Beck disease (Tan et al., 2010). Selenium exists in two forms: inorganic (selenite and selenate) and organic (selenomethionine and selenocysteine). The organic form is vital for functions related to reproduction, DNA synthesis, thyroid hormone metabolism, and protection against infection and oxidative damage (Zhu et al., 2019).

Selenium supplementation can be beneficial in preventing viral diseases and alleviating immune disorders. However, its use has limited toxicity at high doses. Interestingly, selenium nanoparticles (SeNPs) exhibit lower cytotoxicity than other forms such as organic and inorganic selenium (Zhang et al., 2008; Zhang et al., 2001). Moreover, compared to other oxidation states (Se^+IV and  Se^+VI), SeNPs demonstrate excellent bioavailability (Torres et al., 2012). The bioavailability of nanoparticles improves due to their resistance to unfavorable pH values, digestion, and enzymatic cleavage (Yao et al., 2015). This has led to increased interest in the use of selenium nanoparticles in biomedical research. In many clinical studies, selenium nanoparticles have been used as alternatives to traditional forms of selenium. They confirmed a decrease in cytotoxicity with increasing size of selenium nanoparticles (Skalickova et al., 2017). This nanoform of selenium is biologically highly active (Zhang et al., 2005) has a stronger detoxifying effect on heavy metal exposure (Ikemoto et al., 2004), and can prevent DNA oxidation (Huang et al., 2003).

The focus of this review is on studies on the synthesis of selenium nanoparticles using various chemical and biological methods. In addition, we discuss the biological applications of SeNPs in the animal field and investigate the antioxidant properties and safety issues related to the use of selenium nanoparticles in animal models.

Synthesis of selenium nanoparticles

There have been various methods for producing selenium nanoparticles, including physical methods, Chemical and green synthesis using microorganisms or plant extracts.

Physical synthesis

Physical methods use a top-down approach in which larger molecules are either crushed or ground into smaller ones (Harris et al., 2019). Physical methods include hydrothermal treatment, irradiation, and pulsed laser ablation (Dhawan et al., 2021). The deposition method, or pulsed laser ablation (PLA), is a well-known physical method for synthesizing selenium nanoparticles. This method controls the size of nanoclusters using laser parameters, such as wavelength and pulse duration (Marine et al., 2000).

Chemical synthesis

In chemical methods, the synthesis is bottom-up. In this method, selenium nanoparticles were produced by reducing a selenic acid solution with ascorbic acid, in the presence of polysaccharides. Polysaccharides influence the formation and stabilization of Se nanoparticles (S. Y. Zhang et al., 2004). Chemically produced selenium nanoparticles have several advantages such as biocompatibility, biodegradability, and nontoxicity (Bezerra et al., 2008; Saini et al., 2015). These advantages allow selenium nanoparticles to be used in nutritional and biomedical applications as well as in drug delivery systems (Rinaudo, 2006).

Biological synthesis (Green synthesis)

A green synthesis approach for selenium nanoparticles has recently attracted attention. It offers improved biocompatibility and stability compared with chemical methods that require reducing and stabilizing agents that can be toxic and hamper their use in biological systems (Bisht et al., 2022).

Selenium nanoparticles have been synthesized using a variety of organisms, including bacteria, fungi, algae, and plant extracts. These organisms convert toxic metal ions into non-toxic ones (Bhainsa & D’Souza, 2006; Song & Kim, 2009). Thus, they act as both bio-reductants and stabilizers for SeNP nanoparticles.

Recent studies have highlighted the advantages of green synthesis of SeNPs using plant extracts, ease of synthesis, and feasibility for biological applications (Ikram et al., 2021; Korde et al., 2020). Therefore, there is an enormous body of literature on the biosynthesis of SeNPs (Shoeibi & Mashreghi, 2017; Tugarova et al., 2020; Wang et al., 2019; Xu et al., 2019).

Antibacterial

Selenium nanoparticles have been found to exhibit significant antibacterial activity against a variety of bacteria. Studies have confirmed their role in inhibiting the growth of E. coli, Streptococcus pyogenes, P. aeruginosa, and S. aureus. For instance, selenium coatings on polycarbonate medical devices significantly inhibited S. aureus growth by 27% after 72 hours compared with an uncoated polycarbonate surface (Wang & Webster, 2012). Green synthesized selenium nanoparticles in the 100–150 nm size range showed potent inhibition of five microbes, including S. aureus and Proteus sp. E. coli, Klebsiella sp., Pseudomonas sp. (Menon et al., 2019).

Other studies have also explored the antibacterial effect of Se nanoparticles. Stevanović et al., (2015) showed that SeNPs exhibited significant antibacterial activity against gram-positive bacteria, S. aureus and S. epidermidis.

Alagawany et al., (2021) tested chemically synthesized selenium nanoparticles against three gram-negative bacteria (E. coli, P. aeruginosa, and S. enterica) and three positive strains (L. monocytogenes, B. cereus, and S. aureus). They observed the maximum inhibition zones in three gram-positive bacterial strains. In same context, Filipovi et al., (2021) investigated the antimicrobial activity of SeNPs on eight standard bacterial strains. They proved that SeNPs provide better antimicrobial activity against Gram-positive bacteria.

SeNPs also show anti-biofilm activity against pathogens such as Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, and Escherichia coli (Khiralla & El-Deeb, 2015). In same context, SeNPs have been proposed as an alternative to eradicate bacterial biofilms, reducing the possibility of bacterial antibiotic resistance (Hernández-Díaz et al., 2021). Selenium nanoparticles were also tested against antibiotic-resistant bacteria, multidrug-resistant E. coli (MDR), and methicillin-resistant S. aureus (MRSA), with SeNP concentrations of∼25 ppm effectively inhibiting the growth of antibiotic-resistant bacteria (Geoffrion et al., 2020).

Antifungal activity

Selenium nanoparticles show broad antifungal activity against various fungi, suggesting that they are good weapons against fungal infectious diseases (W. Lin et al., 2021). In a recent study, chemically synthesized selenium nanoparticles were tested against animal pathogenic Candida strains using the disk diffusion method. Chemically synthesized selenium nanoparticles (Che-SeNPs) demonstrated satisfactory antifungal activity against all tested fungal strains, with concentrations ranging from 50 to 800 µg/mL. Among the strains tested, C. albicans was found to be the most sensitive to Che-SeNP (Alagawany et al., 2021). Moreover, Shakibaie et al. (2015) showed that Se NPs exerted a potent inhibitory effect on Aspergillus fumigatus and Candida albicans. In the context of Candida albicans biofilms, a study investigated the mechanism by which Se NPs inhibit Candida albicans. Selenium nanoparticles penetrate pathogens and destroy the cell structure by substitution with sulfur (Guisbiers et al., 2017).

Anti parasitic activity

Various studies have highlighted the role of SeNPs in controlling several parasites such as leishmania, coccidia, intestinal schistosomiasis, and Toxoplasma gondii (Beheshti et al.; 2013; Dkhil et al., 2019; Alkhudhayri et al., 2020 and Shakibaie et al., 2020). These findings suggest that SeNPs could be used as dietary supplements with strong antiparasitic effects (Lin et al al., 2021).

Anti-aflatoxin 

However, little research has been conducted on the alleviating effects of selenium nanoparticles on aflatoxicosis. A recent study has shown promising results in using selenium nanoparticles to counteract the harmful effects of aflatoxicosis in male albino rats. The study found that a higher dosage of Se-NPs (0.5 mg/kg) was more effective in eliminating aflatoxin B1 from the liver tissues of the affected rats compared to a lower dosage (0.3 mg/kg) (Hassan et al., 2020).

Antiviral

Research has shown that selenium is effective against a number of viruses, including influenza virus and hepatitis C virus (Beck et al., 1995; Li & Beck, 2007; Verma et al., 2008; Stone et al., 2010; Himoto et al., 2011 and Wang et al., 2012)

As for influenza viruses, selenium nanoparticles showed antiviral activity against influenza viruses. SeNPs inhibit H1N1-induced apoptosis in MDCK cells (Y. Li et al., 2018). Moreover, it has been found that it inhibits ROS-mediated p53 signaling pathways in lung tissue (Wang et al., 2020). In contrast, SeNPs did not significantly inhibit H9N2 infection (Hossein et al., 2015).

Recently, few studies have examined the role of NanoSe in COVID-19. This is due to the proven effect of selenium intake in the treatment of COVID-19 (Moghaddam et al., 2020). A significant disinfection activity of 87.5% against SARS-CoV-2 coronavirus was observed using SeNP-printed polyester fabric (Elmaaty et al., 2022).

While Selenium has been found to be effective against a variety of viruses, its toxicity raises significant concerns. This makes nano-selenium a preferred choice as an antiviral agent due to its lower toxicity compared to bulk selenium. The median lethal dose (LD50) of NanoSe in mice is less than that of organic selenium and selenite (Wang et al., 2007; Zhang et al., 2001). The low toxicity and biocompatibility of nano-selenium make it a promising candidate for antiviral applications. For instance, surface-modified SeNPs containing oseltamivir (OTV) have shown potential as effective anti-H1N1 antiviral drugs. They interfere with the H1N1 influenza virus in host cells by inhibiting the activity of hemagglutinin and neuraminidase, and their superior antiviral properties help limit drug resistance (Li et al., 2017). Furthermore, Se-NPs are used as drug delivery systems against EV71 virus infections and provide opportunities to control EV71 infections (Lin et al., 2020).

Immunomodulatory effects

Immunity is severely compromised by the lack of selenium in the diet. Selenium deficiency can weaken the immune response of calves infected with foreign pathogens. In contrast, selenium supplementation increases IgG and IgM levels in calves and supports their immunity (Reffett et al., 1988).

Recent studies have explored the impact of adding selenium nanoparticles to the diet and its potential effects on humeral immunity in response to vaccination in broilers. It was found that dietary supplementation with selenium nanoparticles at concentrations of 0.15 ppm positively affected humeral immunity in broilers, with the birds showing HI titers compared to those in the Newcastle control-vaccinated group (Azab et al., 2019). Moreover, supplementing the diet with SeNPs at a dosage of 0.1 mg/dose significantly increased the expression of interleukin 2 (IL2), interleukin 6 (IL6), and interferon (IFN) in blood cells, which was accompanied by a significantly high antibody titer against HPAI H5N1 (Yehia et al., 2022). Similarly, glycine nano-selenium was found to enhance the effectiveness of the H9N2 avian influenza vaccine by significantly increasing immunoglobin indices and mRNA levels of certain interleukins in the liver, lungs and spleen (Ren et al., 2022).

Selenium nanoparticles have been shown to modulate both innate and adaptive immunity, suggesting their potential use in treating various immunological responses associated with infectious diseases. For instance, dietary chitosan-selenium nanoparticles were found to boost immunity against Aeromonas hydrophila infection in zebrafish (Xia et al., 2019). In a similar vein, another study demonstrated that Se NPs enhances intracellular Mtb-killing efficiency by promoting host antibacterial immunity and inducing apoptosis, autophagy, and antibacterial M1 polarization of host cells (Pi et al., 2020).

Vaccines adjuvants

Selenium nanoparticles have recently attracted attention and have been used as adjuvants in vaccines. Few studies on this topic have investigated their possible immune-boosting effects. Selenium nanoparticles serve as novel adjuvants to enhance the immune response against killed whole-cell Vibrio cholerae in a mouse cholera model. The addition of selenium nanoparticles to this vaccine elicited strong protective immune responses in a mouse model (Raahati et al., 2020).

Ranjbariyan et al. (2023) added synthetic SeNPs as a co-adjuvant to the vaccine formulation against MRSA infection. The SeNPs showed a significant increase in cellular and humoral immunity. Higher levels of total IgG and increased levels of cytokines were observed. This suggests that selenium nanoparticles, as good co-adjuvants, enhance the immune response against methicillin-resistant Staphylococcus aureus.

Selenium nanoadjuvants have been used in SARS-CoV-2 vaccines. Se nano-adjuvant-based vaccines induce the activation of innate immune cells. Nanoadjuvant-based Se vaccines can induce Th1-dependent immunity and superior antigen-specific neutralizing antibodies with a high titer and potency to fight pseudovirus infections. Selenium nano-adjuvants are universal drug candidates that can boost the immune response against serious diseases (Lai et al., 2023).

Drug delivery

Se NPs is considered a promising option for drug delivery. They can carry drugs at high concentrations, significantly enhancing their effects (Guan et al., 2018) and increasing drug potency (Chen et al., 2008). In line with this, an injectable Se NP nanosystem has been developed to load anticancer drugs like sorafenib (Zheng et al., 2019) and boost solubility of oridonin (Pi et al., 2017).

selenium-lipid nanocarriers loaded with ciprofloxacin have proven to be effective drug delivery systems for preventing pulmonary infections in interstitial lung diseases (Liu et al., 2019). They also improve isoniazid intracellular Mtb killing efficiency and aid in intracellular pathogen clearance (Pi et al., 2020).

Growth performance and body weight gain

The high surface area to volume ratio of selenium nanoparticles provides a large surface area for interaction with mucosal tissues and cells. This property improves their absorption into the mucosal surface, thereby extending the residence time of these particles in the intestine (Kassim et al., 2022). Thus, selenium nanoparticles showed improved growth performance and feed conversion ratio compared with the bulk forms of selenium. This has been demonstrated in various animal models; for example, poultry supplemented with nano-selenium had a higher body weight and a lower feed conversion rate (P<0.05) than poultry fed inorganic or organic selenium (A. A. Abdel-Wareth et al., 2022; Ahmadi et al., 2018; Jayanthi et al., 2018; Azab et al., 2019; Zhou & Wang, 2011).

In fish, Se nanoparticles are required for the optimal growth of striped catfish (Pangasianodon hypophthalmus). Based on the regression analysis of the FCR data, Se nanoparticles are recommended at a level of 1.02 to1.11 mg/kg diet (El-Sharawy et al., 2021). Furthermore, fish fed dietary Se nanoparticles at 1 mg/kg daily, every other day showed improved growth rates and feeding efficiencies (Abd El-Kader et al., 2020).

Studies have shown that the performance of growing rabbits can be significantly improved by supplementing their diet with 0.3 mg nano-Se/kg (Abd Allah et al., 2020; Qin et al., 2016), and 25 and 50 mg nano-selenium/kg (Sheiha et al., 2020). Similarly, the inclusion of Che-SeNP in rabbit diets has been found to significantly enhance feed intake and feed conversion ratio (Abdel-Wareth et al., 2019; Sheiha et al., 2020).

In the case of ruminants such as goats and lambs, supplementation with Se nanoparticles has been observed to have a positive impact on body weight and average body weight gain, as demonstrated in studies by Shi et al. (2011) and Yaghmaie et al. (2017).

Antioxidant activity of selenium nanoparticles

Various abiotic stresses can induce the overproduction of toxic reactive oxygen species (ROS), leading to the destruction of vital nutrients such as carbohydrates, proteins, and lipids, and consequently causing a range of diseases (Kumar et al., 2020). The cellular and tissue-level benefits of selenium nanoparticles have piqued the interest of researchers globally due to their biomedical applications. They also play a crucial role in reducing free radical concentrations, thereby preventing oxidative DNA damage under both in vivo and in vitro conditions (Battin et al., 2011). This review outlines the impact of nano-selenium on antioxidant levels and lipid profiles across various animal models.

Rabbits. 

El-Badry et al., (2019) found that the use of nanoselenium in rabbits significantly enhanced the total antioxidant capacity in their blood and mitigated the negative effects of heat stress by lowering the levels of blood malondialdehyde. Similarly, Sheiha et al., (2020) observed that New Zealand rabbits subjected to heat stress for 56 days showed marked improvements when fed a diet enriched with biologically synthesized nano-selenium at feeding rates of 25 or 50 mg/kg (50–400 nm). The selenium nanoparticles (SeNPs) led to a reduction in glutathione and catalase activities compared to the heat stress group. Furthermore, both nitric oxide and malondialdehyde levels saw a significant decrease in the groups treated with selenium nanoparticles compared to other groups.

Broilers

Boostani et al., (2015) found that broilers supplemented with 0.3 mg/kg of nano selenium showed a significant increase in the levels of reduced glutathione and the activity of glutathione peroxidase (GSH-Px), and a decrease in malondialdehyde levels compared to both controls and stressed birds. Similarly, El-Deep et al. (2017) observed that poultry consuming a diet with nano selenium (0.2–0.3 mg/kg) showed a significant improvement in serum-reduced glutathione (GSH) activity.

Shirsat et al., (2016) supplemented chickens under oxidative stress with biogenic selenium nanoparticles (100 nm) for 42 days along with enrofloxacin. The selenium nanoparticles (SeNPs) had beneficial effects on cellular and humoral immune response activities, and there was an evident increase in enzymatic and non-enzymatic antioxidants after reduced EFX treatment.

Di-(2-ethylhexyl) phthalate (DEHP), a common artificial pollutant found in the environment, can cause biological damage to various organs through oxidative stress, enhancing the degree of oxidative damage and apoptosis in chicken liver cells. However, adding 1 mg/kg of nano-selenium to the feed reversed these changes. Experimental results indicated that nano-selenium counteracts the toxic effects of DEHP via the PI3K/AKT pathway (Li et al., 2021).

Quails

Alagawany et al. (2021) reported that in quail, groups fed a diet supplemented with 0.4 g/kg of selenium chemical nanoparticles during the fattening period (15 weeks of age) experienced a significant improvement in performance, lipid profile, antioxidant indices and immunity. and a reduction in intestinal pathogens.

Goats

(Shi et al., 2011) showed improvements in the antioxidant status of male goats fed SeNPs compared with those fed selenium yeast and sodium selenite. Elevated levels of serum superoxide dismutase, catalase (CAT) and glutathione peroxidase (GSH-Px).

Pigs

A previous study found that feeding selenium nanoparticles (30-70 nm) at a rate of 0.5 mg/kg over a period of 25 days led to an increase in the levels of superoxide dismutase, catalase, immunoglobulin G, and immunoglobulin A, and a decrease in malondialdehyde in both serum and liver (Liu et al., 2022) .

Rats

Amin et al., (2017) found that selenium nanoparticles can protect against liver damage caused by an overdose of paracetamol. This protection is achieved through the enhancement of liver function and oxidative stress mediated by catalase, SOD, and GSH, and a reduction in hepatic DNA fragmentation, a marker of cell death in rats. In a another study, Kokila et al.  (2017) highlighted the antioxidant properties of selenium nanoparticles. It's worth noting that the shape and size of nanoparticles can significantly influence these properties. For instance, hollow spherical selenium nanoparticles have been shown to exhibit antioxidant properties ( Wang et al., 2007). Therefore, plant-derived selenium nanoparticles are more effective in preventing ROS-mediated diseases caused by oxidative stress.

Donkeys

The impact of selenium nanoparticles on heat shock proteins (HSPs) and the gene expression of HSP90, which are additional indicators of oxidative stress, was examined. Enhanced oxygen metabolism leads to the production of reactive oxygen species (ROS), and intense training in trotting horses can result in oxidative stress, ROS generation, and subsequent damage to lipids, proteins, and DNA. Besides adaptive changes in protective enzymes like SOD, catalase, and GPx, oxidative stress in cells is known to boost the production of stress proteins or HSPs. The expression of HSPs is a defensive mechanism against disturbances in cellular homeostasis and integrity during physical activity. A study was conducted on the effect of orally administering selenium nanoparticles (0.5 mg kg − 1) for 10 days on the gene expression of HSP90 during intense training in donkeys (Kinnunen et al., 2005; Kojouri et al., 2013).

Kojouri & Sharifi. (2013) investigated the influence of selenium nanoparticles on blood urea nitrogen in donkeys. High concentrations of urea are known to induce oxidative stress and DNA damage in cells. The study revealed that oral administration of selenium nanoparticles led to changes in blood urea nitrogen, creatinine, and total protein during intense exercise in donkeys, significantly increasing the serum selenium concentration after supplementation with selenium nanoparticles. The creatinine concentration in both the experimental and control groups significantly increased at 2 hours post-exercise rest and rapidly decreased in the experimental group after 72 hours of post-exercise rest. A similar pattern was observed with changes in blood urea nitrogen in the control group; its concentration significantly increased at 2 hours of rest post-exercise compared to the group dosed with selenium nanoparticles. These findings may elucidate the positive effects of dietary supplementation with selenium nanoparticles on serum changes in blood urea nitrogen levels and blood creatinine in response to intensive training of donkeys. The beneficial effects of selenium nanoparticles could be attributed to the integration of selenium into proteins such as selenocysteine and its protective role against oxidative tissue damage.

Fish

Li et al. (2023) suggested that Nano-Se has a protective effect against gut damage caused by heat stress in rainbow trout. This is achieved by enhancing the activity of antioxidant enzymes (catalase, GPX, thioredoxins (TRX)), promoting protein repair, reducing inflammatory responses, and restoring the composition of the intestinal microbiota. In a similar vein, Sun et al. (2022) showed that 5.0 µg/mL SeNPs could potentially serve as hepatocyte-protective therapeutic agents. They found that these nanoparticles synergistically boost the expression of GSH-Px and SOD activity, thereby protecting hepatocytes from heat stress in rainbow trout.

Toxicity and safety of selenium nanoparticles:

Selenium nanoparticles have recently garnered significant interest due to their lower toxicity compared to dissolved ionic selenium species (Ikram et al., 2021). The toxicity of these nanoparticles can be further reduced through green synthesis or modification. While numerous animal studies have been conducted to assess the toxicity of selenium nanoparticles, our understanding of their toxicological effects remains limited (Bisht et al., 2022). For instance, in vivo toxicity studies based on LD50 data have shown that the toxicity of selenium nanoparticles is approximately four to six times lower than that of SeMet, Se-Met, and SeCys (Wang et al., 2007, Zhang et al., 2005; Zhang et al., 2008). The higher toxicity of selenite, SeCys2, and SeO2 is attributed to their ability to initiate the oxidation of thiol groups in proteins (Kim et al., 2003), which can disrupt the activity of essential enzymes containing sulfhydryl groups. In comparison to selenite, Nano-Se has proven to be superior as it significantly increases hepatic glutathione peroxidase levels, reduces the production of malondialdehyde (a product of lipid peroxidation), and enhances the activity of antioxidant liver enzymes such as superoxide dismutase and catalase (Zhang et al.2005).

Nanoselenium, when compared to sodium selenite, is less toxic and more biocompatible, exhibiting a range of beneficial properties such as catalytic performance, adsorption strength, surface activity, chemical stability, and high antioxidant activity (Boostani et al., 2015 ; Skalickova et al., 2017). Furthermore, the majority of studies comparing the toxicity of Se and nano-selenium concur with the lower toxicity of nano-selenium. In same context, Qin et al. (2016) discovered that a low dose of nano-selenium at a dose of 0.3 mg/kg body weight administered over a 48-day period in rabbits did not have any harmful effects and did not significantly alter blood biochemistry or liver enzyme activity. Moreover, Hosnedlova et al. (2018) noted that comprehensive toxicological studies demonstrated that 20-60 nm nano-selenium and Se-methionine in supranational amounts (30 and 70 μg Se/kg bw) reduced Se accumulation in whole blood, liver, and kidneys in a dose-dependent manner compared to controls. However, at diet-related Se concentrations (1000 mg Se/kg body weight), no improvement in bioaccumulation in blood and tissue was observed with nano-selenium, unlike with the Se-methionine form.

Abbas, (2021) pointed out that various animal species exhibit different responses to the effects of selenium and selenium nanoparticles. Given the sensitivity of these species to water pollutants, the toxicity of nanoparticles has been primarily studied in aquaculture. The toxicity of Se nanoparticles in aquaculture is well-documented and validated in recent research, suggesting that nanoforms of Se are notably less toxic than inorganic Se salts. Dawood et al. (2021) noted that selenium nanoparticles can accumulate in the environment and be ingested by fish, leading to significant bioaccumulation. However, controlled studies have also shown that nano-selenium can enhance the productivity of aquatic animals and improve their health. Similar to mammals, the toxicological effects in fish are also dependent on the dose, chemistry of the nanoparticles, and duration of exposure.

Mohammadinejad et al., (2015) emphasized the need for extensive research to devise less toxic and cost-effective synthetic methods, and to comprehend the role of nanoselenium in cancer therapy, chemotherapy, and radiotherapy to modulate their efficiency and cytotoxicity. Bionic or green-synthesized and modified nanoparticles have been reported to enhance health effects in animal models and reduce toxicity, owing to the unique properties of bionic selenium. Biogenic nano-selenium holds potential for use as an anti-TB and antiviral agent, as well as a drug delivery system. The toxicity of nanoselenium is influenced by several interrelated parameters such as nanoparticle size, nanoselenium chemistry, dose, and exposure time, which collectively affect the biological response of the organism. In a related study, Mal et al., (2017) examined the toxicity of biogenic nanoselenium formed by anaerobic granular sludge biofilms on zebrafish embryos in comparison with selenite and chemogenic nanoselenium. The biogenic nano-Se exhibited an LC50 value of 1.77 mg⋅L−1, making it 3.2 times less toxic than selenite and 10 times less toxic to zebrafish embryos. Nano-Se stabilized with bovine serum albumin was found to be less toxic than chemogenic. In this context, biogenic methods offer greater advantages over chemical reduction methods due to their higher biocompatibility and lower cytotoxicity. Therefore, they are considered promising therapeutic agents for cancer treatment and antioxidant and antimicrobial applications (Bisht et al.,2022).

However, there is limited literature on the interaction of nanoselenium with the immune system, gastrointestinal tract, bioaccumulation in muscle, and other indirect targets of selenium. Jia et al., (2005) conducted a study on the sub-chronic toxicity of different forms of Se in Sprague-Dawley rats (both sexes). The rats were fed diets containing varying concentrations of individual compounds (0, 2, 3, 4, and 5 mg⋅kg−1 Se) for a duration of 13 weeks. Significant abnormal changes were observed in body weight, hematology, clinical chemistry, relative organ weights, and histopathological parameters at Se doses of 4 and 5 mg ⋅ kg − 1. The toxicological evaluation of SeNPs has primarily focused on the performance of the antioxidant system in terms of body weight and bioaccumulation in the liver, kidneys, and heart.

Due to its large surface area and small size, nanoselenium appears to be more reactive and exhibits better biodistribution in organisms compared to other forms of selenium. Rats that ingested 0.5, 1.5, 3.0 and 5.0 mg Se/kg (sublethal doses of nanoselenium) for 28 days with a size of 100 nm showed damage to the liver parenchyma and intestinal epithelium and reduced ALT activity (Urbankova et al., 2021).

The toxicity of selenium nanoparticles has been examined in various animal models. Han et al., (2021) studied the effects of sublethal doses of nano-selenium (100 nm) at doses of 0.3 mg/kg diet during a 30-day treatment in lactating dairy cows, which resulted in increased plasma Se and GPx levels and decreased mRNA expression levels of several enzymes and selenoproteins. Li et al. (2021) found that sheep taking 5 mg nanoselenium/kg bw for 30 days exhibited changes in various blood parameters and immune markers, with the nano-selenium group (40 nm) showing lower values than the control. Xun et al. (2012) reported changes in rumen chemistry when sheep were fed selenium nanoparticles at 4 mg/kg b.w. for 25 days.

Gangadoo et al. (2020) found that broilers fed inorganic selenium at various doses for 29 days showed lower bioavailability of selenium in certain tissues and increased accumulation in detoxification organs when compared to organic selenium.

Li et al., (2008) discovered that medaka fish (Oryzias latipes) exposed to nano-selenium for 10 days at a dose of 100 µg Se⋅L−1 showed greater toxicity due to hyperaccumulation compared to those exposed to the same amount of Na2 SeO3.

Gallego-Gallegos et al. (2013) conducted a study on the toxicity of nano-selenium using a 10-day exposure to aquatic and dietary larvae of Chironomus dilutus. They found that even the lowest concentrations of Se0 and nano-selenium tested resulted in selenium bioaccumulation, particularly as SeMet. Inhibition of larval growth was also observed at higher concentrations due to dietary and aquatic exposure. However, these studies primarily used chemically produced nanoparticles. Recent research indicates that the toxicity of selenium is dependent on its method of production, with biogenic nano-selenium being less toxic than chemogenic selenium. For instance, Khiralla and El-Deeb (2015) found no significant toxicity of nano-selenium biosynthesized by B. licheniformis when tested using Artemia salina larvae as a model organism in the toxicity assessment of nanoparticles. Similarly, Rajabi et al., (2015) observed no toxicity in Artemia larvae exposed to nano-selenium up to 100 µg⋅mL−1.

Conclusion and future prospects

Selenium is a vital trace mineral with many antimicrobial biological activities; however, its use to combat microbes has been restricted owing to toxicity concerns. Selenium nanoparticles are predominantly biologically synthesized. Thus, nano-selenium is an excellent option for overcoming this limitation. Additionally, they are both bioavailable and biocompatible. This review highlights the importance of selenium nanoparticles in fighting many types of bacterial, viral, fungal, parasitic, and animal infections. It also plays a role in increasing body weight and enhancing antioxidant parameters in various animal models. It is also used as a drug delivery agent, vaccine adjuvant, and immunomodulatory. Toxicity issues related to selenium nanoparticles are also discussed in this review. Extensive research is needed in the near future to develop synthetic methods to obtain more biocompatible and less toxic selenium nanoparticles. In addition, the urgent need for Further clinical studies using animal models are required to investigate the toxicological effects of selenium nanoparticles.