​Selenium Dioxide Nanoparticles and Its Applications

Selenium is basically a chemical element that comprises of the atomic number 34 and Se the symbol. However, when combined with oxygen it becomes selenium dioxide commonly known as SeO2. When SeO2 is present in the form of nanoparticles which are tiny particles, hard to see with the naked eye, they become selenium dioxide nanoparticles. The nanoparticles are used for various purposes but more specifically in the field of medicine.

Their excellent characteristics make them so usable and authentic in industries almost all over the world. However, they are prepared in three ways, chemically, physically, and biologically all of which have their own significance.

Introduction

A chemical compound, selenium dioxide, has a formula SeO2. Selenium has many usually encountered compounds, this colorless solid is one of them. Although, the atomic number of selenium is 34 and its symbol is Se, as it is a chemical element. This nonmetal has the characteristics that are intermediate between the elements that are below and above in the periodic table, for instance, tellurium and sulfur, and also some similarities with arsenic, making it considered as a metalloid rarely. In the crust of Earth, it occurs as a pure ore compound or in its elemental state. Jöns Jacob Berzelius discovered selenium in 1817 from Ancient Greek σελήνη (selḗnē) "Moon", and he compared the new element’s similarity with the tellurium that’s already discovered (named for the Earth).

Selenium

Selenium replaces sulfur partially in metal sulfide ores where it is also found. Selenium is commercially formed as a byproduct when these ores are being refined, usually during production. There is some information on the mineral that is pure selenite or selenide but they are rare. Pigments and glass making are selenium's chief commercial uses. Selenium is utilized in photocells and is a semiconductor. Silicon semiconductor devices have been majorly replaced by them for applications in the electronic field. In one type of fluorescent quantum dot and some types of DC power surge protectors, selenium is still being utilized.

Properties

Solid selenium dioxide is a 1-D polymer. Alternating atoms of oxygen and selenium are in the chain. A terminal oxide group is possessed by each Se atom and each of them is pyramidal. 162 pm is the terminal Se-O distance and 179 pm is the bridging Se-O bond lengths. There is an alternation in the relative stereochemistry at Se along the polymer chain. At high temperatures, selenium dioxide is present as monomeric species whereas, in the gas phase, it is present as oligomeric species and dimers. Like sulfur dioxide, the monomeric form attains a bent structure with a 161 pm bond length. In the argon matrix of low temperature, dimeric form is separated and it possesses a centrosymmetric chair form according to vibrational spectra. A trimer [Se(O)O]3 is given by SeO2’s dissolution in selenium oxydichloride.

Monomeric SeO2

It is a polar molecule. It has a 2.62 D dipole moment pointed from the 2 oxygen atom's midpoint to the selenium atom. Sublimation of the solid occurs readily. Vapour resembles decayed horseradishes and possesses a revolting odor at extremely low concentrations whereas at very high concentrations, their odor resembles horseradish sauce and when inhaled, it can burn the throat and nose. TeO2 is a cross-linked polymer while SeO2 is a 1-dimensional chain and SO2 acts like a molecular chain.

Selenium dioxide is an acidic oxide, and selenous acid is formed when SeO2 is dissolved in water. The terms, selenium dioxide and selenous acid are often utilized interchangeably. Selenium dioxide forms a reaction with base for producing selenite salts that contain SeO2−3 anion. For instance, sodium selenite (Na2SeO3) and water are produced when selenium dioxide forms a reaction with sodium hydroxide.

Chemical synthesis of selenium nanoparticles

In chemical synthesis terms, ascorbic acid reduces selenious acid in polysaccharides’ presence for preparing SeNPs. Carboxymethylcellulose, acacia gum, glucomannan, and CS, are polysaccharides. CS is biodegradable, pH-sensitive, non-toxic, non-immunogenic, biocompatible, and charged positively, making CS an appropriate component to be administered orally for a broad range of applications in nutrition and biomedicine. Because of its capability to develop medication delivery systems, it has been searched broadly in the pharmaceutical industry.

Carboxyl, hydroxyl, and reactive amino groups are present in polysaccharides' molecular structure and they have a significant effect on SeNP’s growth, stabilization, and formation. Various biophysical methods, for instance, electron microscopy are utilized for performing ex-situ characterization after NPs synthesis. Huge stability has been shown by the obtained monodisperse spherical selenium particles and they can be utilized as dietary additives.

Selenium encapsulation

Zhang et al. investigated selenium encapsulation into CS nanoparticles and its effects. According to the studies, this encapsulation into CS nanoparticles is a good way to deliver selenium to cells in which the retention of selenium increases, thereby lessening the chance of damaging the DNA. In low selenium level case, development of NP–selenium compound systems majorly enhances selenium’s bioavailability and simplifies selenoproteins’ expression.

Ionic-induced synthesis

Ionic liquid-induced synthesis in presence of polyvinyl alcohol stabilizer is another example of SeNPs’ chemical preparation. In ionic liquid-induced synthesis, sodium selenosulfate acts as a selenium precursor, forming spherical SeNPs in the 76-150 nm size range.

Organic synthesis

In organic synthesis, one of the significant reagents is SeO2. Glyoxal is obtained on paraldehyde’s (acetaldehyde trimer) oxidation with SeO2 and cyclohexane-1, 2-dione is obtained on cyclohexanone’s oxidation. On oxidation, the starting material of selenium lessens to selenium and then is precipitated as a red amorphous solid which can be filtered off easily. The reaction and oxidation of such kinds are known as Riley oxidation. Also, it is famous as a reagent for a reaction known as "allylic" oxidation. In general terms, it can be described like this;

R2C=CR'-CHR"2 + [O] → R2C=CR'-C(OH)R"2 where R", R', R, may be aryl or alkyl substituents.

As a colorant

The red color is imparted to the gas by selenium dioxide. In order to counteract the color, it is utilized in a lesser amount because of iron impurities and for creating glass that’s colorless. It will impart a deep ruby red color if it is in a larger amount. In photographic development, it is utilized as a toner. In some of the cold-bluing solutions, the active ingredient is selenium dioxide.

Safety

Although selenium is one of the very significant elements, if you ingest selenium in more than 5 mg/day then it can result in nonspecific symptoms.

Applications

Selenium nanoparticles as a food additive

Due to lower toxicity and high bioavailability as compared to organic and inorganic forms, selenium’s nanoform gains more attention as the organic compounds are less toxic than the inorganic ones. The size of the selenium nanoparticles (SeNPs) determines their biological characteristics. For instance, greater activity is shown by the smaller particles.

The nanoparticle's cellular intake is also affected by the size of the particle. For instance, in comparison with the Vitro absorption of 1-10 μm particles, the Vitro absorption of 0.1 μm particles was 2.5-6 times higher, respectively. When it comes to making dietary supplements, the particle should be of particular morphology and size, along with an appropriate encapsulation material. A system that’s based on the ingestion of the food supplements encapsulated into nanoparticles exhibits a significant potential of improving supplement’s bioavailability with a chance of enhancing their characteristics, like resistance to adverse pH, enzymatic cleavage, and digestion.

Advantage of nano-selenium

Nano-selenium has many advantages, one of them being the possibility of utilizing selenium in zero oxidation state (Se0), presenting remarkable bioavailability and low toxicity in comparison with other oxidation states (Se+VI, Se+IV). Although, it is extremely unstable and can be altered into an inactive form very easily. However, if we encapsulate it into appropriate nano-vehicles, we can obtain its stabilization, for instance, chitosan (CS). A broad amount of applications are possessed by the nanoscale selenium in biomedicine. The effect of nanoscale selenium on oxidative stress reduction is pretty much known. Hollow spherical SeNPs and their antioxidant characteristics are demonstrated by Gao et al, lessening selenium toxicity's risk.

Nano-Se has its potential as a chemopreventive agent other than its usage as an antioxidant with lessened chances of toxicity. According to the conclusions of various studies, nano-Se is more beneficial in cancer chemoprevention as an anticancer drug, and as an anticancer drug delivery carrier. Nano-Se’s antifungal activity and antimicrobial effect have been shown in many studies. Moreover, there are good documentations on nano-selenium’s protective effects against metal intoxication. Also, there is a confirmation of nanoscale selenium’s immunostimulatory effect. Also, nano-selenium has a very good and advantageous effect on various physiological functions.

Biogenic SeNPs

The antiprotozoal effect of Nano-Se was explained along with its remarkable capabilities. Leishmania major causes localized lesions typically of cutaneous leishmaniasis which according to in vivo and in vitro studies, can be treated by a novel therapeutic agent, known as biogenic SeNPs. There were also descriptions of SeNPs’ anti-leishmanial activities against Leishmania infantum. As compared to selenium dioxide (SeO2), an enhanced growth-inhibitory effect is seen on promastigotes by SeNPs.

Mechanism of the passage of NPs through the intestinal mucosa

One of the most cost-effective and suitable supplementation methods is the oral administration of nanoparticles. Although, if absorption barriers are present in the digestive tract, it will make the absorption of nanopartcles tougher and more difficult. In order for nanoparticles to be absorbed, it is important for overcoming the 2 barriers in the GI tract, one is the intestinal mucosa and the other is the mucus that covers the intestinal mucosa.

Intestinal epithelium and passing through it

The intestinal epithelium has M cells, goblet cells, primarily enterocytes, and a series of specialized cells. Enterocytes allow the absorption of nutrients and controls the transition of macromolecules. Goblet cells secrete mucus, covering the intestinal mucous membrane's adherent layer. The main purpose is to prevent any kind of chemicals or potential pathogens from entering the intestinal mucosa and to maintain a different pH between the intestine’s mucosal surface and the lumen.

Transcellular (through the cells) and paracellular (between adjacent cells) are the two ways in which nanoparticles can travel across the intestinal epithelium. The tightness of junctions between epithelial cells and the narrow region of intercellular spaces are the two reasons for the restriction of paracellular way under physiological conditions. 0.3-1.0 nm is the pore diameter. Transcytosis is the process of NPs transcellular transport, starting with endocytosis in cells’ apical membrane. Afterward, the transportation of nanoparticles is done via transcellular way and then they are released on the basolateral pole.

Nano-Se as an antioxidant

As compared to selenium's other chemical forms, a better antioxidant capability is possessed by Nano-Se while lessening selenium toxicity’s risk. SeNPs’ antioxidant characteristics were displayed by Wang et al. that showed lower toxicity in comparison with selenomethionine (SeMet). Elemental Nano-Se and its effect on glutathione peroxidase’s activity (GPx) was studied by Zhang et al in weanling pig’s liver as compared with selenium’s inorganic form. At 0.5-1.0 mg Sekg−1 diet concentration rate, the animals had GPx higher activities in Nano-Se’s form and not in the form of Na2SeO3.

Effect of SeNPs on reproductive performance

Lipid peroxidation is used by oxidative stress for affecting spermatozoa’s fertility potential, resulting in dysfunctional sperm. Deficiency of selenium results in the production of abnormal mitochondria in goat spermatozoa. Semen GPx activity, testicular activity, and concentration of selenium in testes can be increased by Nano-Se supplementation. Also, it can prevent the integrity of the membrane and protect the tight arrangement of mitochondria’s mid-piece. Tests were done on goats to study and investigate the effects of the presence of elemental Nano-Se in the diet on the GPx activity, ejaculate quality, and testes ultrastructure. They inserted animals with nano-Se in 0.3 mgkg−1 declared selenium dose from weaning to sexual maturity for 12 weeks.

According to the results, the group that was supplemented with nanoscale selenium showed a major increase in the selenium level in testes and a significant increase in the activity of GPx and ATPase in the ejaculate too as compared to the control group. Selenium’s addition didn’t affect the quality of the ejaculate (pH, motility, density, and volume). In comparison to the SeNPs group, abnormal spermatozoa’s percentage in the control group was very high. Transmission electron microscopy was used to see that the plasma membrane of the sperm was damaged in selenium-deficient goats, along with the abnormalities in the spermatozoa’s mitochondria midpiece.

Nano-Se for improving fetal growth and development of hair follicle

Improvement of the development of hair follicles and promotion of the fetus growth was demonstrated in Wu et al’s study along with the significance of selenium’s maternal administration at a nano size. A decrease in the generation of reactive oxygen species (ROS) was caused because of a rise in the antioxidant defense, resulting in IGF-1 and its receptor’s (IGF-1R) upregulation, as they both are very important for improving both characteristics.

The positive effects of SeNPs

SeNPs have a good influence on the wool quantity in cashmere goats. When 0.5 mgkg−1 diet was administered till 110 days, it started to manifest in their fetus with considerably higher expression levels of IGF-1R, IGF-1, and GPx genes in the skin. At 110 days, they observed increased IGF-1, increased selenium concentrations, increased superoxide dismutase activities, and increased GPx, in both blood serum and skin. Also, they observed very low production of MDA (malondialdehyde) in both serum and skin, affecting the status of the antioxidant in fetuses’ skin, majorly increasing the number of their secondary hair follicles. ROS's low level possibly upregulates IGF-1R and IGF-1, as they affect hair follicle development in the fetus. Also, the group that received SeNPs, showed significantly high weights of placenta and fetus as compared to their weights in the control group.

Antibacterial and antiviral effects of SeNPs

Their remarkable antimicrobial activity is the reason that they gained such considerable attention. Selenoprotein’s integral component, selenium, controls some of the important biological processes like specific enzyme modulation and ROS elimination. Selenium is also one of the very important trace elements and it is regulated by cellular redox homeostasis. The deficiency of selenium can lead to susceptibility to viral infections. A huge amount of attention was gained by SeNPs because of their antiviral capability, and some of their other benefits like remarkable activity and low toxicity. One of the efficient realizable methods is the administration of SeNPs in order to enhance the body’s immune response.

Anticancer effects of SeNPs

As drug carriers and in cancer chemotherapy, SeNPs have displayed excellent anticancer activity, along with high potential. SeNPs’ anticancer effects are mediated by their capability of inhibiting the growth of cancer cells through the induction of cell cycle arrest at the S phasewhich is mediated by the elF3 protein complex's deregulation. According to the latest study, a significant role is played by the cell membrane in SeNPs-induced toxicity in the cancer cells. Cancer cells’ biomechanical characteristics are changed by the treatment of SeNPs, specifically, the Young modulus, and the adhesion force of the cancer cells is also decreased. Other than excellent anticancer efficacy, SeNPs also display better selectivity between cancer cells and normal cells as compared to Se+IV at similar concentrations. Cancer cells can specifically internalize SeNP

s through endocytosis and can activate apoptotic signal pathways to induce cell apoptosis.

Nano-Se as an anticancer drug

As compared to other selenium compounds, nano-Se has higher anticancer efficacy. Glutathione S-transferase’s (GST) induction by selenium is the key mechanism for the chemopreventive effect. GST activity improved much earlier in Nano-Se administration than in selenite and SeMet.

Effect of SeNPs on the oxidative stress parameters

There was a comparison made in the study between the nano-Se’s effect on the oxidative stress parameters and the organically bound selenium’s effect. A comparable efficiency is possessed by nano-Se in increasing plasma GPx activity as SeMet in mice but displayed much lower toxicity with respect to short-term toxicity, LD50, and acute liver injury. According to the results, we can administer nanoscale selenium as an antioxidant with a lessened chance of toxicity of selenium.

Heat shock proteins

There were investigations on SeNPs effect on HSPO90 gene expression and heat shock proteins (HSPs) as the additional oxidative stress parameters. ROS formation was induced by the amplified oxygen metabolism. If the trotter horses are intensively trained, it will result in oxidative stress, DNA, protein, lipid damage, and ROS formation. If Oxidative stress is given to cells, it can induce amplified fabrication of HSPs or stress. During physical exercise, HSPs expression is one of the adaptive mechanisms against the disturbance in cellular integrity and homeostasis.

Nano-Se in treatment of metabolic disorders

There was a recent development of promising nanocarriers for antidiabetic supplement’s oral delivery for potentiating its curative effect. Selenium-coated nanostructured lipid carriers (SeNLCs) were designed by Yin et al to improve the oral bioavailability and to strengthen berberine’s hypoglycemic action. On oral administration of berberine-loaded SeNLCs to the rats, the hypoglycemic effect was considerably higher and berberine’s bioavailability was greatly enhanced as compared to berberine-loaded nanostructured lipid carriers. Both of the characteristics were enhanced because of selenium nanocarriers' intestinal absorption and better-sustained drug release.

Treatment of fatty liver disease

In treating fatty liver disease (FLD), nano-Se is efficacious. Fatty liver is a metabolic disorder’s sign which affects 50% of dairy cows nearly after calving, and because of the deposition of ectopic fat in the liver. The fatty liver can result in total damage to the liver damage and death. The mortality can go up to 25 percent if not properly treated. Nano-Se’s application may be good in treating this disease. Hegedüs et al studied Nano-Se’s effect in male Wistar rats on FLD therapy, which resulted in a low inflammation level and free radical’s release in sick animals than the control group. Samples’ historical analysis and transmethylation ability confirmed it. The bioactive nanoscale selenium is efficient and effective.

Conclusion

Selenium dioxide nanoparticles are abundantly being used and specifically in the field of medicine. There are a lot of diseases and problems which are being treated with the help of these nanoparticles. It is due to their remarkable performance that they are being used at such a large scale for all the positive outcomes. All these positive outcomes are playing their role in taking Se-nanoparticles to more directions in which they can excel and show their characteristics.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901133/

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/selenium-dioxide

https://www.sciencedirect.com/science/article/pii/S2211379721002564

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