Review on bio-selenium nanoparticles: Synthesis, protocols, and applications in biomedical processes

1 Introduction

Nanomaterials are composed of numerous molecule atoms that can occur in spherical clusters, layered, tube shape, or cuboid shape. Metallic and metalloid nanoparticles (NPs) have attracted special interest because of their utility in catalytic, photocatalytic, anticancer, biosensor, absorbent, and biomedical applications [1]. Selenium (Se), silicon (Si), cerium (Ce), silver (Ag), titanium (Ti), ferric (Fe), gold (Au), and zinc (Zn) metal NPs hold a distinctive position in the field of nanotechnology because nanomaterials (NPs) present an exceptional opportunity as theragnostic agents and have huge potential as transport media for small interfering ribonucleic acid (siRNA), proteins, chemotherapeutics, and other substances. Selenium nanoparticles (SeNPs) are important NPs that have been the subject of most research. In 1817, Jöns Jacob Berzelius discovered Se. Three main categories can be used to categorize NPs synthesis techniques: physical, chemical, and bioassisted. Physical and chemical processes of NPs synthesis, such as sol–gel technology, solvothermal synthesis, chemical reduction, and ion sputtering, are widely used techniques. Nonbiogenic methods have disadvantages and render NPs unsuitable for biomedical and dietary applications, whereas biogenic methods are secure, affordable, environmentally friendly, and nontoxic [2]. Biological agents, such as bacteria, viruses, fungi, yeast, plant extracts, and actinomycetes, are used in bioassisted methods to synthesize NPs. Metal NPs and their oxides are mostly produced through biogenic NPs synthesis, which also utilizes microorganisms or plant extracts as templates [3]. NPs synthesized using biological techniques are more advantageous and ecologically benign, and it is possible to optimize the size and yield of NPs. Optimization improves the synthesis and yield of SeNPs, as well as enhances their applicability in many biomedical domains [4].

1.1 Role of selenium in the metabolism of living organisms

Selenium is an inert element that is colorless, nontoxic, and in its “zero” oxidation state. It was named after the Greek word “Selene,” which means moon. The Se atomic number is 34, which is placed in the 6th Group of the periodic chart. It has numerous oxidation states, such as 2⁺, 4⁺, 6^+, and 2, and plays a major role in daily life. It is an essential cofactor as it has the potential to damage the liver, skeletal muscle, kidneys, heart, and testes [2].

Selenoproteins have several crucial functions, including the control of immunomodulatory activity and sperm motility [5]. The human genome contains 25 selenoprotein genes. Several enzymatic antioxidants, including selenoprotein P (SELENOP), thioredoxin reductase (TXNRD), and glutathione peroxidase (GPX), incorporate Se into selenocysteine (SEC). Se acts as the redox center for the biological action of these enzymes. Monomethylated Se, selenomethionine, and sodium selenite (Na₂SeO₃) are significant Se-containing chemicals that can function as anticancer medicines (mostly chemopreventive) through various methods [6]. Other features of Se include biological properties, such as anticancer, antioxidative, and free radical scavenging potentials, and other applications. Trace elements are in high demand as dietary supplements, like Se, which can enter the body through food consumption, and the primary food sources of Se as fish and vegetables. Se intake varies across the world depending on factors including the amount of Se in each country’s soil, pH of the soil, the category of crop cultivated, and how much Se vegetables can be stored and consumed [7]. Humans with Se deficiency have higher rates of hypothyroidism, cardiovascular illness, and immune system dysfunction.

Selenium in their nanostructures has many beneficial properties, such as enhanced biological activity, drug carriers, and enhanced bioavailability. SeNPs are synthesized using numerous physical procedures, including UV radiation, laser ablation, and hydrothermal treatments. Biological systems are also known as biological factories for the production of distinct SeNPs because they use a detoxifying process to reduce selenites/selenates to nanoselenium [8]. Various microorganisms, fungi, algae, and plants have been described as potential factors/agents of SeNPs, as shown in Figure 1. Microbes can transform the ionic form of metals into elemental NPs. When the ionic form of the metal enters cells, enzymatic/biological reduction occurs primarily.

Figure 1

Biosynthesis of SeNPs and their uses.

A reliable extraction method is necessary for the release of NPs from cells. The synthesis of Se0 is influenced by the concentration of bacteria (B. subtilis) and, particularly, by the incubation period. Extending the incubation period increases the microbial enrichment of selenium, resulting in the production of SeNPs that are bioavailable and nontoxic. These NPs are derived from ionic selenium (SeO₃ ²⁻) and have nutritional benefits for both humans and animals. SeNPs synthesized using biotic sources are less hazardous than bulk SeNPs synthesized by chemicals. The extract biomolecules function as SeNPs reducing agents and stabilizers. SeNPs are less poisonous, more reactive, and have excellent bioavailability compared with other forms [9]. SeNPs have several applications. Figure 2 illustrates the drug delivery mechanism using SeNPs. The process begins with the drug’s encapsulation within SeNPs. These NPs exhibit enhanced cellular uptake due to their small size and surface characteristics. Upon reaching the target site, SeNPs release the drug in a controlled manner, ensuring sustained therapeutic effects. Specific intracellular conditions, such as pH changes or the presence of certain enzymes, often trigger the release mechanism. This targeted delivery minimizes side effects and maximizes the drug’s efficacy at the desired location.

Figure 2

Mechanism of drug delivery using SeNPs.

2 Biosynthesis of SeNPs by bacterial organisms and their applications

Microorganisms are a major source of biofactories for the synthesis of bioNPs. Some microbes, including yeasts, bacteria, and fungi, are employed to make SeNPs because they can flourish and survive in particular Se proportions, as well as convert harmful ions into specific NPs [10]. In this overview, we focused on the source of bacterial SeNPs, and their applications are presented in Table 1. Many researchers have worked on the bioconversion of Se into NPs using microorganisms, which are the best option among all microbes for NPs synthesis, due to their rapid rate of growth, simplicity in management, low budget, and high output [11]. Bacteria can reduce selenate or selenite to SeNPs by enzymatic/nonenzymatic and aerobic/anaerobic methods, and they are created because of this biotransformation, as shown in Figure 3 [12].

Figure 3

Mechanism of the biosynthesis of SeNPs using bacteria.

Many aerobic and anaerobic bacteria, for example, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, can reduce inorganic selenium (SeO₃ ²⁻/SeO₄ ²) to extra/intracellular SeNPs. Bioavailable SeNPs (5–200 nm) activate selenoenzymes that help the body defend against free radicals [13]. The research carried out by Torres et al. [14] explored the antioxidant effects of SeNPs derived from the Pantoea agglomerans strain UC 32. Under aerobic conditions and RT, selenite is biologically reduced to yield bioactive SeNPs smaller than 100 nm. Alkaline lysis was used to separate and purify the NPs. l-Cysteine was used to stabilize the pure NPs (4 mM). SeNPs possess stronger antioxidant activity than selenite. SeNPs that have been stabilized through biological synthesis and possess sizes smaller than 100 nm may be an alternative food supplement with important antioxidant qualities for human health. Selenium nanospheres prepared by biomimetic synthesis using the bacterial strain JS11 can be used as a biosensor for the toxicity of NPs [15]. Bacteria can be utilized for the process of bioremediation in water bodies that have been contaminated by poisonous selenite, where P. aeruginosa converted selenite into biomimetic SeNPs [13]. Biogenic protein-encapsulated SeNPs were synthesized from Lactobacillus casesii known as capped SeNPs, which have low cytotoxicity and considerable antioxidant and anticancer effects [16].

Bacillus species obtained from sources of clean water are processed in the synthesis of extracellular nano-selenium, confirming its cytotoxic and antibacterial properties. All examined microorganisms were susceptible to the antibacterial action of SeNPs. SeNPs had a good minimum bactericidal concentration (MBC) against P. aeruginosa. The cytotoxicity of SeNPs against the A549 cell line, a human non-small lung cancer cell line, was assessed using the MTT test. The findings revealed that the IC50 value was 3 µg/mL. SeNPs treatment leads to ET/AO staining of cells, providing additional clarification. From this, we deduced the freshwater bacterium Bacillus sp. [17]. Figure 4 shows the anticancer mechanism of SeNPs isolated from bacteria. Cancer cells undergo apoptosis when SeNPs produce reactive oxygen species (ROS), mess up the mitochondrial membrane potential (MMP), and initiate the caspase pathways. Additionally, SeNPs inhibit cell proliferation by modulating signaling pathways and inducing cell cycle arrest. This multifaceted approach targets and kills cancer cells effectively, showing that SeNPs from bacteria could be used as a new anticancer drug.

Figure 4

Anticancer mechanism of SeNPs isolated from bacteria.

Alam et al. [18] synthesized SeNPs from the probiotic bacterium Lactobacillus acidophilus and observed that the extracellular proteins contributed to the reduction and stability of Se ions in the form of LA SeNPs. LA SeNPs showed increased antimicrobial properties against resistant bacterial pathogens. The bacteria present in the intestines provide many health advantages, including lower cholesterol, relief from diarrhoea, and strengthening of the immune system. A study showed that 96 fruit- and flower-origin LAB strains are responsible for the metabolism of Se. The bacteria’s ability to grow in the presence of 5 ppm selenite while also accumulating and reducing selenite to produce seleno amino acids was verified, and the utilization of lactic acid bacteria resulted in the transformation of Se into volatile selenite compounds and SeNPs [19].

By using Bacillus subtilis, Ullah et al. published a study on the production and analysis of SeNPs [9]. The synthesis of SeNPs reduction in B. subtilis increased gradually when a selenium-enriched medium (600 µg/mL) was used. B. subtilis BSN313 converted soluble, toxic, and transparent Se ions into insoluble red SeNPs. In terms of scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABST), SeNPs demonstrated good antioxidant activity. SeNPs have potential antibacterial activities against P. aeruginosa, Staphylococcus aureus, and E. coli. An investigation by Kashiwa et al. [20] showed that Bacillus sp. is capable of bioconverting selenate to selenite and selenite to selenium element, but the bioconversion rate of selenate is higher. Bacillus sp. SF1 may utilize various organic acids and sugars as carbon sources to carry out selenate reduction. Optimization of green SeNPs synthesis and assessment of antifungal activity against fungal infection in the mouth caused by the yeast Candida albicans were studied by Safaei et al. [21]. SeNPs were produced by a green method using Halomonas elongata. The findings indicated that the produced NPs exhibited superior performance and inhibited the growth of C. albicans. Because of the successful use of SeNPs in antifungal activities, mouthwash formulations can be incorporated as antibacterial agents to help prevent and treat a variety of oral disorders.

3 SeNPs biosynthesis using algae and its applications

Phycosynthesis of SeNPs using microalgae is a promising method for the biosynthesis of SeNPs. In this review, photosynthesized SeNPs and their applications are presented in Table 2. One of the studies used the cell-free extract from Spirulina platensis for the preparation of SeNPs. SeNPs synthesized from microalgae have antimicrobial effects against pathogens isolated from food, such as Salmonella typhimurium and S. aureus. The antibacterial properties were attributed to the decrease in the size of SeNPs. To produce efficient bioactive compounds to combat dangerous bacterial species, a novel, simple phytosynthesis of SeNPs utilizing S. platensis is recommended [22]. Photosynthesized SeNPs from S. platensis have improved antioxidant activity compared to that of Na₂SeO₃ [23].

Polysaccharides from S. platensis have been used for the synthesis and stability of SeNPs. Researchers have established a straightforward solution-phase approach for functionalizing Spirulina polysaccharides (SPS with SeNPs). According to these results, the utilization of SPS as a surface decorator may prove to be a useful approach for increasing the cellular absorption and anticancer effectiveness of NPs. More research into SPS SeNPs as chemopreventive and chemotherapeutic drugs against human cancers is warranted [24]. Figure 5 depicts the SeNPs biosynthesis process using algae. Algal extracts are mixed with Se precursors, initiating NPs formation through reduction and stabilization. This eco-friendly method leverages the natural biochemical properties of algae to produce SeNPs with potential applications in biomedicine, environmental remediation, and agriculture. The resulting SeNPs are characterized by their size, shape, and bioactivity, highlighting the efficiency and sustainability of algae-mediated biosynthesis.

Figure 5

Biosynthesis of SeNPs using algae.

Afzal et al. [25] screened SeNPs production for the size of the NPs, reaction duration, and bioactivity of crude extracts of 20 cyanobacteria. Using SOR scavenging assays and DPPH, the antioxidant properties of the top five cyanobacteria, Anabaena variabilis, Phormidium sp., Oscillatoria sp., Gloeocapsa gelatinosa, and Arthrospira indica, were evaluated. The highest antioxidant activity was demonstrated by SeNPs produced by A. indica. Gas chromatography mass spectrometry (GC-MS) and Fourier transform infrared (FTIR) spectroscopy were employed to identify various functional groups and biological compounds present in the fluid extraction of A. variabilis and would have affected the process of reduction in SeNPs were identified. B SeNPs exhibited higher antioxidant properties, anticancer and antimicrobial activities coupled with their biocompatibility, indicating a greater likelihood of their use in biomedicine compared to C SeNPs [26]. Hnain et al. [27] described the synthesis of intracellular SeNPs from Synechococcus leopoliensis, which occurred inside thylakoid bands near the center of the cells rather than between the cytoplasm and thylakoid membrane.

SeNPs prepared from the aqueous extract of Sargassum angustifolium are small particles (approximately 40 nm) with a colloidal spherical morphology. Algae-coated and -uncoated SeNPs (Penaeus vannamei, a serious pathogen) were challenged against Vibrio harveyi, and the results demonstrated that algae-coated SeNPs had better antibacterial action against V. harveyi. The cytotoxicity of various doses of these SeNPs on shrimp hemocytes and human lymphocytes showed a lack of toxicity in both human and shrimp cells [28]. Nannochloropsis oceanica algae were used for the synthesis of SeNP-enriched biomass for aqua feed uses, as a feed additive, having favorable benefits on the health of the fish and potential growth implications in animal wellbeing [29].

Haematococcus pluvialis, a significant industrial resource for natural astaxanthin, was utilized for SeNPs bioaccumulation, which in turn greatly enhanced astaxanthin synthesis, antioxidant enzyme activity, and intracellular hydrogen peroxide levels [30]. SeNPs synthesized from Chlorella vulgaris, a single-cell green alga, by intracellular bioaccumulation could be an antioxidant feed for human health and aquaculture [31]. SeNPs are made from two marine microalgae Halimeda opuntia and Kappaphycus alvarezii, with potential antibacterial agents against diseases in the significant fish Vibrio parahaemolyticus and crustacean V. harveyi diseases [28].

4 SeNPs biosynthesis using fungi and its application

The mycosynthesis of SeNPs refers to the process of synthesizing SeNPs using fungal or fungal extracts (Table 3). This method utilizes the unique properties and capabilities of fungi to reduce Se ions to form SeNPs. Yeast is a fungus belonging to the fungus kingdom. Yeast can also be used for the synthesis of SeNPs. Yeast, similar to fungi, possesses the capacity to engage with metal ions and transform them into NPs through the process of reduction. Nematospora coryli is a species of yeast that belongs to the family Saccharomycetaceae, is commonly found in various habitats, including soil, plants, and insects, and is used for the low-cost biosynthesis of SeNPs. SeNPs have antioxidant and anticandida properties [32].

According to the morphology and genetic information of the ITS1-5.8S ITS2 16 Recombinant Deoxyribonucleic acid (rDNA) sequence, an aquatic yeast species has been determined and identified as a special kind of strain Rhodotorula mucilaginosa that can help to produce SeNPs in amorphous form. The impact of several factors, including the concentration of biomass, precursor concentration, and incubation time, has been studied during the biosynthesis of NPs [33]. Figure 6 illustrates the biosynthesis mechanism of SeNPs using fungi. Fungal enzymes lower selenium ions, which makes stable SeNPs that could be used in many areas. The role of yeast-derived SeNPs in immune regulation and antioxidative activity in cyclophosphamide-induced rats was studied. The study showed that SeNPs, in addition to protecting the mouse spleen, liver, and kidney, dramatically increased the levels of IgM, IgA, and IgG. They also significantly reduced the immunosuppression caused by cyclophosphamide. SeNPs, which are synthesized from yeast, can potentially replace antibiotics in animal husbandry because they improve the resistance of animals to oxidative stress and infectious illnesses when utilized as a trace element feed supplement [34].

Figure 6

Mechanism of biosynthesis of SeNPs using fungi.

Filamentous fungi have been explored for SeNPs synthesis. Various species of filamentous fungi have shown the capacity to decrease selenium ions and aid in the synthesis of SeNPs. In a previous study, 75 fungal colonies were examined to determine their capacity for synthesizing SeNPs. Among the isolates, four strains, Aspergillus terreus, Aspergillus ochraceus, Fusarium equiseti, and Aspergillus quadrilineatus, were cultured from twigs of Acalypha indica, Ricinus communis, and Hibiscus rosasinensis, respectively. These strains possess the capability to generate SeNPs with in vitro antioxidant and antibacterial properties. The SeNPs derived from these four strains exhibited robust antifungal and antibacterial properties when evaluated against a range of human and plant diseases. In addition, SeNPs produced by each strain demonstrated promising antioxidant capability, with IC₅₀ values below 200 µg/mL [35]. Zare et al. [36] identified the extracellular production of tiny SeNPs by fungi. This study elucidated the synthesis of SeNPs utilizing a culture of a fungal strain derived from soil samples, which was subjected to centrifugation to collect the supernatant. The synthesis of extracellular SeNPs by cell-free culture medium has not yet been studied. A . terreus culture supernatant was added to a selenium ion solution, and the obtained SeNPs were spherical with an average diameter of 47 nm.

According to Amin et al. [37], gamma radiation can improve the mycosynthesis of SeNPs by Penicillium citrinum. The biogenic SeNPs have demonstrated promising potential for application in the field of medicine as agents with antioxidant and anticancer properties. Some fungi, including Alternaria alternata and A. terreus, can biosynthesize SeNPs. Fungi, including F. oxysporum, can synthesize SeNPs that have an average size of 78 nm. Fungal families possess mycelia, which have a greater surface area compared to other bacteria. This characteristic enables them to effectively facilitate the interaction between fungal reducing agents and metal ions. As a result, they can produce significantly high amounts of secreted proteins, thereby enhancing the rate of synthesis of NPs [38]. Zhang et al. [39] showed that SeNPs are produced through the biosynthesis of the fungus Mariannaea sp. Several proteins that adhere to the external surface of NPs can function as inherent stabilizers.

Sodium selenate can be bioreduced to SeNPs using the fungus A. alternata’s culture filtrate. α-Se enhances the function of the selenoenzyme glutathione peroxidase and reduces free radicals. Moreover, it has been discovered that they have significant uses in the rectifier, solar cell, exposure meter, xerography, and glass industries [40]. Mushrooms are regarded as the most important element in epicurean cookeries worldwide because of their distinctive flavor and reputation as a culinary wonder. Although there are more than 2,000 types of mushrooms in nature, approximately 25 are generally considered edible, and only a small number are commercially available. Mushrooms possess important medical qualities, such as detoxifying, antiallergic, antiparasitic, hepatoprotective, antifungal, cardiovascular, antidiabetic, antioxidant, and antibacterial properties [41]. Edible mushroom extract (EME) from Agaricus bisporus is an effective and ecofriendly safe precursor for biogenic production of SeNPs. These SeNPs are 8 nm in size, have good antioxidant properties, and do not have any cytotoxic effects against the prostate cancer cell line [42]. Some species, such as the fungus Pleurotus tuberregium, have also been reported to synthesize and stabilize SeNPs using polysaccharides [43].

5 SeNPs biosynthesis using plants and its application

SeNPs biosynthesis using herbal extracts is a better alternative method for the synthesis of SeNPs. The plant synthesis approach uses reducing agents that are easily available, nontoxic [44], inexpensive, biodegradable, and environmentally friendly [45]. Table 4 provides an overview of biogenic SeNPs that have been produced from different plant sources and showcases their wide range of applications. The easy accessibility of raw materials, such as agricultural waste and fruit peels, and the fact that some of these plants have long-standing and useful pharmacological applications, is a determining factor in the manufacture of SeNPs [46]. One of the important reasons for the utilization of plant materials is that they are rich in alkaloids, flavonoids, polyphenols, polysaccharides, and saponins, and are effective reducing and stabilizing agents. Synthesized by plants, SeNPs are highly valuable in the biomedical industry due to their exceptional biocompatibility [47]. Fardsadegh et al. [48] examined the antifungal and antibacterial properties of SeNPs and their production using Aloe vera leaf extract. They demonstrated that SeNPs have potent antibacterial activity against Gram-positive and Gram-negative bacteria such as E. coli and S. aureus, as well as antifungal efficacy against the plant pathogenic fungi Collectotrichum coccodes and Penicillium digitatum. Zebaree et al. [49] used the leaf extracts of Asteriscus graveolens to synthesize SeNPs. The prepared NPs were cytotoxic to HepG2 cells. Figure 7 illustrates the process by which plants synthesize SeNPs. It highlights plant roots’ uptake of Se ions from the soil, followed by their transport to leaves and other aerial parts. Within plant tissues, enzymes and metabolites help these ions go through processes that reduce and form new ions, which create SeNPs. This mechanism showcases the role of plants in environmentally friendly NPs synthesis. Portulaca oleracea extract served as a biocatalyst in the synthesis of SeNPs from Na₂SeO₃. Phytosynthesized SeNPs demonstrated various biological activities that varied with dose, such as promising action against causative bacteria and other species of Candida with different minimum inhibitory concentration (MIC) levels. P. oleracea-based SeNPs have strong potential as anticancer, antiinsect, antiviral, and antimicrobial agents in biomedical and pharmaceutical industries. SeNPs showed antiviral activity against HAV and CoxB4, and the as-formed SeNPs had a huge impact against different instar larvae such as I, II, III, and IV of Culex pipiens, and they were highly effective against various insect species [50].

Figure 7

Mechanism of SeNPs biosynthesis using plants.

The extract of Clausena dentata leaf-conjugated SeNPs had the ability to kill mosquito vectors by insecticidal action. C. dentata was used to prepare SeNPs, which were then examined for their ability to kill the fourth instar Anopheles stephensi larvae, Culex quinquefasciatus, and Aedes aegypti. These findings imply that the production of SeNPs from the leaf extract of C. dentata may represent an important, environmentally friendly strategy for early prevention of mosquito vectors [51].

Diospyros montana aqueous extract was used to carry out the plant-mediated synthesis of SeNPs using a simple precipitation technique. The potential antioxidant properties of the biosynthesized SeNPs were demonstrated by DPPH and decreasing power activities. Gram-positive S. aureus and Gram-negative E. coli (bacteria) and Aspergillus niger (fungus) were among the microorganisms that were significantly resistant to the antibacterial effects of the NPs suspension (fungi). The cytotoxicity of SeNPs against MCF7 human breast cancer cells was assessed. SeNPs were shown to have anticancer characteristics, in that they were capable of suppressing cell proliferation in a dose-dependent manner [52].

Selenium plays a dual role in the development of chronic disorders, such as diabetes, as it has low toxicity and may liberate Se by gradually releasing bioactive substances after ingestion. There is currently a great deal of interest in the nanopharmacology field in studying the role in personal healthcare. SeNPs were produced from a fluid extraction of popular herbal tea leaves, specifically Java tea (Orthosiphon stamineus). The cytotoxicity of the SeNPs produced using green methods was evaluated using skeletal muscle cell lines. Preclinical experiments are now being conducted to demonstrate the ability of SeNPs to mimic insulin [53].

The synthesis of SeNPs is carried out by utilizing pelargonium leaf extract following microwave irradiation. The antibacterial properties of the synthesized SeNPs were tested using E. coli and S. aureus as test organisms, which showed that the produced NPs had a stronger antibacterial activity against the bacteria. In addition, greater antifungal activity against C. coccodes was observed for the synthesized SeNPs against P. digitatum and C. coccodes [54]. Na₂SeO₃ was combined with an extract of alcohol from the guava leaves (Psidium guajava) to produce SeNPs. Both Gram-positive and -negative bacteria were resistant to the antimicrobial properties of the synthesized NPs. Scanning electron microscopy (SEM) revealed that SeNPs damage the bacterial cell structure. The toxicity of the hepatoblastoma (HepG₂) and Chinese hamster ovary (CHO) cell lines was examined. The NPs were found to have strong antibacterial capabilities and biocompatibility [55].

Without the use of any toxic substance, SeNPs that are tested against acetaminophen cause harm in the kidneys and liver of rats. Green SeNPs were synthesized using Spermacoce hispida as a carrier for s-allyl glutathione. These NPs were designed to provide nephroprotective and hepatoprotective effects against acetaminophen toxicity [56]. Owing to their impact on redox adjustment within the human body, SeNPs have garnered growing interest over the past few decades. Lower bioactivity, bioavailability, and biocompatibility are the result of the propensity of SeNPs to cluster into large masses. SeNPs stabilization and biological activity are greatly influenced by their surface capping agents. In this study, green tea extracts were used as reductants in a green synthesis technique to create SeNPs with Lycium barbarum polysaccharide caps. Functionalized NPs showed high antioxidant activity, including the ability to scavenge DPPH and ABTS free radicals. Additionally, SeNPs dramatically reduced H₂O₂-induced mortality in PC12 cells. The possible application of SeNPs as dietary components, supplements, or neuroprotectants with antioxidant properties [57].

Fardsadegh et al. [54] used response surface methodology (RSM) methods to determine the optimum conditions for the synthesis of NPs using Pelargonium zonale leaf extract. E. coli and S. aureus were utilized as model organisms for the antibacterial activities of the synthesized SeNPs, which revealed that the NPs synthesized exhibited enhanced antibacterial efficacy against Gram-positive organisms. The possible application of SeNPs as dietary antioxidants, supplements, or neuroprotective agents. Additionally, P. digitatum and C. coccodes were targets of the improved antifungal action of the synthesized SeNPs. According to Santanu et al. [58], the reduction in the capacity of orange peel extract is indirectly related to the amount of time needed for the growth of Na₂SeO₃ into SeNPs. SeNPs were examined for their antialgal action, and it was discovered that they were successful in preventing algal blooms.

Theobroma cacao was suggested by Mellinas et al. [59] as a capping and reducing substance for SeNPs production. ABTS and reducing ferric antioxidant power (FRAP) techniques further demonstrate that SeNPs exhibit good antioxidant performance, with prospective applications in various industries, including food, medicine, and pharmaceuticals. In a dose-dependent manner, Menon et al. [60] compared the inhibition ratio of SeNPs synthesized from ginger extract to that of ascorbic acid, which was used as a reference drug in DPPH tests. The presence of biomolecules aids in the breakdown of Na₂SeO₃ into SeNPs, which are their elemental forms. Zingiber officinale was used to manufacture SeNPs. According to research on the MIC of SeNPs against Proteus sp., their bactericidal action can only be established at a specific concentration. DPPH assay was used to assess antioxidant activity. Therefore, it is necessary to create a biological agent that is efficient, affordable, and compatible with pharmaceutical and industrial applications.

The flower of Bougainvillea spectabilis Willd was used for the biological yielding and characterization of SeNPs. To create SeNPs, this study examines the bioreduction behavior of the flower extract derived from Catharanthus roseus (Apocynaceae family) and Peltophorum pterocarpum (Caesalpiniaceae family). The environmentally friendly method used to create SeNPs is straightforward and suitable for large-scale manufacturing and biomedical applications [61]. Allamanda cathartica flower extract is used in the biosynthesis of SeNPs, and the study evaluated the capacity of Brassica campestris seeds to promote germination under high salt concentration, as well as their ability to inhibit the growth of phytopathogenic bacteria, namely, those that cause diseases in mustard seeds. SeNPs, which have little or low toxicity, have beneficial effects on plant growth, and can be a suitable antimicrobial agent for treating diseases in plants caused by the aforementioned phytopathogens [62].

Biosynthetic and environmentally related technologies for the synthesis of NPs and bio-nanotechnology have been developed as a merger of biotechnology and nanotechnology. An assessment of the antioxidative and antibacterial characteristics of SeNPs by using Delonix regia and Nerium oleander flower extracts. The SeNPs significantly suppressed the activity of Aeromonas hydrophila, E. coli, and P. aeruginosa. Moreover, a potential mechanism of antibacterial activity was proposed. Using a hydrogen peroxide assay, the produced SeNPs also demonstrated a higher antioxidant efficacy than the benchmark [63]. Anu et al. [64] suggested that SeNPs can be produced by utilizing a green technique, and a fluid medium extraction of Allium sativum displayed significant cytotoxicity against the Vero cell line. Through intercalation and groove binding, SeNPs created a fluid extract of A. sativum that disturbed the structural integration of DNA in the calf thymus. The current experimental data show that SeNPs directly interact with DNA, which may be a plausible pathway for increasing their anticancer potential, in addition to their known antioxidant activities. Additionally, it creates a new platform for SeNPs research that will allow for the development of more effective and side-effect-free SeNPs complex anticancer drugs [65].

Jay and Shafkat [3] documented biogenic synthesis of SeNPs using an extract derived from A. sativum. Using the well diffusion method, SeNPs were tested for their antimicrobial effects against B. subtilis and S. aureus. This method effectively created SeNPs with antibacterial activity against harmful microorganisms. Extraction of fenugreek seeds was performed by Ramamurthy et al. [66] to prepare SeNPs. Human breast cancer cells were used to evaluate the cytotoxicity (MCF7) on SeNPs. SeNPs were found to limit cell proliferation in a dose-dependent manner. Furthermore, the combination of SeNPs and doxorubicin exhibited superior antitumor activity compared with either agent alone.

The synthesized parameters (duration, Se precursor concentration, temperature, and concentration of the extraction) are addressed together with the properties of the produced product (shape and size stability composition). Through the process of reducing H₂SeO₃ using l-asparagine in a polyethylene glycol solution, Yu et al. [67] created several nanostructures of Se, such as nanoballs, nanorods in multiarms, and nanotubes. NPs with smaller diameters exhibited greater antioxidant activity, according to the ABTS and DPPH scavenging assays of amorphous Se nanoballs. According to the results of the cell viability assay, the amorphous Se nanoballs were not harmful to model cells. A practical approach for creating prospective Se nanostructure applications on a wide scale is provided by our synthetic technology.

The fluid extract of the fruit, Emblica officinalis, was transformed into phytofabricated SeNPs (PF SeNPs) in a rapid, efficient, economical, and ecofriendly method. The potential applications of PF SeNPs, such as their antioxidant, antibacterial, and biocompatible properties, are highly promising. The wide range of antibacterial action of PF SeNPs on food-causing pathogens has also been demonstrated, and it has been discovered to be quite effective against fungi and Gram-positive and -negative bacteria. On treatment with PF SeNPs connected to Na₂SeO₃, caspase 3 and MMP were significantly less affected. The results of the cytotoxicity experiments showed that PF SeNPs were significantly less harmful and safer than Se. In food, medicinal, and pharmaceutical industries, PF SeNPs can potentially be used as antioxidant and antibacterial agents [68].

Ficus benghalensis leaf extract is used for the synthesis of environmentally friendly fluorescent SeNPs. The photocatalytic degradation of MB in a marine environment was carried out using the as-produced SeNPs [69]. Green production of SeNPs using garlic (A. sativum), a plant with significant medicinal value, is carried out. To create SeNPs, garlic extract served as a reducing agent and capping agent. In addition, the cytotoxicity of SeNPs prepared by green synthesis techniques and conventional chemical synthesis was examined. When compared to chemically synthesized SeNPs, biologically generated SeNPs displayed less cytotoxicity and more ecofriendly characteristics based on the CC50 values [64].

Leucas lavandulifolia extract has been used to demonstrate the green production of SeNPs. The stability of NPs and the reduction of Se ions are mostly brought about by phytochemically separated substances and insoluble heterocyclic components such as alkaloids and flavones. Possible antibacterial agents include green-synthesized SeNPs. Owing to the high biological activity of Se, both biological and industrial applications have been developed using metal NPs [70]. Green synthesis of SeNPs was achieved using drumstick leaf extracts. According to a photocatalytic study, SeNPs are effective at destroying the dye used in orange–yellow, and the process of degradation has been suggested. Three different forms of human malignancy have been demonstrated to respond favorably to SeNPs. According to the IC₅₀ values, SeNPs are effective anticancer agents that prevent the proliferation of the three cancer cells. The green-synthesized SeNPs have the potential for further investigation as chemotherapeutic agents for cancer treatment [71].

Biogenic production of SeNPs from the extract of almond peels was performed. The four phases of self-assembly, Ostwald ripening, nucleation, and breakdown are postulated as the mechanisms of SeBr synthesis. Additionally, the antibacterial activity test, in conjunction with MBC and MIC, revealed a specific, selective, and effective action against B. subtilis. The use of biogenic SeBr from fabric-coated cotton can be utilized in operating rooms to lower the incidence related to Bacillus bacteria was shown to be effective, as evidenced by growth kinetics and plate-based assay research. Fabric-coated SeBr had outstanding anti-B. subtilis activity [72].

Biomolecules aid in the breakdown of Na₂SeO₃ into SeNPs, which are their elemental forms. The manufacture of SeNPs utilized Z. officinale. It is necessary to create a biological agent that is efficient, affordable, and compatible with industrial and pharmaceutical uses [60]. By using a wet chemical process, NPs biogenic Se nanorods were created, and citric acid and flavonoids from lemon juice were used to stabilize them. These newly created nanorods are useful for biomedical cellular peroxide sensing in the lower limit using a simple, affordable spectrometric sensing method [73]. Table 5 provides comprehensive information on the shape and size of SeNPs, pointing out their common spherical or rod shape and sizes ranging from a few nanometers to several hundred nanometers. It is important to note that uniformity is essential for ensuring consistent performance in different applications.

Biogenic SeNPs are economically advantageous because of the utilization of natural, renewable resources such as plants and microbes. This reduces the requirement for costly chemicals [74] and intricate equipment. Furthermore, the ecological footprint of biogenic SeNPs is considerably smaller; their production method is environmentally favorable, resulting in limited production of harmful byproducts and a decrease in overall pollution [75]. Biogenic SeNPs typically demonstrate improved effectiveness, superior compatibility with living organisms [76], and increased biological functionality, rendering them more appropriate for medical and environmental uses than their chemically produced counterparts [76].

The microbial reduction method is a straightforward and environmentally conscious approach that utilizes readily available, biodegradable reductants. Similarly, the plant extract synthesis method also has comparable ecological advantages [77].

SeNPs possess several benefits, including a high absorption rate, elevated biological activity, and less toxicity. Moreover, they can be readily absorbed by the human body and transformed into organic selenium [78].

Drawbacks involve the possibility of toxicity arising from the usage of hazardous substances during the process of chemical synthesis. Consequently, there is a growing trend in using environmentally benign chemicals like fungal components and plants to synthesize nanomineral particles [79].

The biological production methods for NPs encounter notable constraints, such as limited scalability [80], control over yield, and consistency in size and shape. Managing the output of NPs is challenging, as it is affected by biological variables and process parameters, resulting in irregular production rates. Furthermore, ensuring consistent dimensions and forms of NPs is essential for their functional characteristics and reliability in applications [81]. However, biological approaches frequently provide diverse morphologies. Synthesizing SeNPs involves trying to make the production scalable (able to increase in size) while carefully controlling the size, shape, and surface properties of NPs [80]. However, achieving these goals is very difficult and presents a significant challenge.

The need for additional research and innovation to enhance the scalability, yield, and standardization of biological synthesis methods for NPs is emphasized by the combination of these intricacies, together with increased production costs and reduced efficiency when compared to chemical methods.

Potential future applications for biogenic SeNPs involve optimizing their utilization in medical applications, such as drug delivery, cancer therapy, and antimicrobial therapies. Additionally, they can be employed in environmental remediation to mitigate pollution and clean wastewater. Furthermore, SeNPs show potential for enhancing agricultural output and crop resilience when incorporated into fertilizers and insecticides. Nevertheless, there are still obstacles to overcome in the process of increasing manufacturing on a large scale while upholding quality standards, dealing with potential long-term toxicity concerns, navigating through regulatory obstacles, and ensuring the stability and effectiveness of SeNPs in different applications.

6 Conclusion and future recommendations

Selenium is a micronutrient supplement responsible for day-to-day metabolic functions in living organisms. Selenium, at an optimal concentration, enhances body immunity, antioxidant activity, and anticancer potential. The bioavailability of selenium as a selenoprotein makes it a perfect biomolecule for essential metabolic functions. This review provides profound information on the synthesis of biogenic NPs using bacteria, algae, fungi, and plants. It mainly focuses on the advantages over conventional methods, including biocompatibility, bioavailability, antioxidant, antidiabetic, antimicrobial, and anticancer effects. Unlike physicochemical methods, the biosynthesis of SeNPs is environmentally friendly and safe. The remarkable properties of biogenic SeNPs possess characteristics that make them very appropriate for a diverse array of biological applications. Their interaction with macromolecules, such as selenomethionine and selenocysteine, helps to fight fatal diseases such as cancer, diabetes, and Alzheimer’s disease. SeNPs have good prospects in the pharmaceutical and food industries. Biogenic SeNPs can be developed as carriers for drugs, cancer therapeutics, as well as antimicrobial, antiviral, and chemotherapeutic agents for many fatal diseases and disorders. Thorough clinical trials are necessary for understanding the role of biogenic SeNPs in their therapeutic effects. Improvement of SeNPs-based therapeutic and delivery systems can result in the betterment of physicochemical properties such as higher stability, bioavailability, and precise release of selenium. For more research on SeNPs derived from biological extraction, the selection of biological extracts should be improved to make the NPs more stable and useful. Additionally, efforts should be made to improve the synthesis methods to allow for large-scale production. Furthermore, comprehensive studies should be conducted to understand the mechanisms involved in the synthesis process and to assess the environmental impact of SeNPs. This will ensure that the production and application of SeNPs in therapeutic settings are sustainable and cost-effective.