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View Article Online Materials View Journal Advances Accepted Manuscript This article can be cited before page numbers have been issued, to do this please use: P. K. Khanna, N. Bisht and P. Phalswal, Mater. Adv., 2022, DOI: 10.1039/D1MA00639H. Volume 01 This is an Accepted Manuscript, which has been through the Materials Number 1 February 2020 Pages 001-200 Royal Society of Chemistry peer review process and has been accepted for publication. Advances Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free rsc.li/materials-advances service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard ISSN 2633-5409 Terms & Conditions and the Ethical guidelines still apply. In no event PAPER XXXXXXX XXXXXXX et al. shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx from the use of any information it contains. rsc.li/materials-advances
Page 1 of 17 PleaseMaterials do not adjust margins Advances View Article Online DOI: 10.1039/D1MA00639H ARTICLE This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Selenium Nanoparticles: A Review on Synthesis and Biomedical Applications Materials Advances Accepted Manuscript Received 00th January 20xx, Neha Bisht,a Priyanka,a and Pawan K.Khanna*a Accepted 00th January 20xx Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. Selenium is a trace and essential micronutrient for the health of human, animals, and microorganisms. Recently, selenium DOI: 10.1039/x0xx00000x nanoparticles (SeNPs) attracted many researchers’ interest due to their biocompatibility, bioavailability, and low toxicity. Therefore, due to their higher bioactivity selenium nanoparticles are largely being used in various biomedical applications. Generally, selenium nanoparticles can be synthesized by physical, chemical, and biological methods. However, the biologically synthesized SeNPs demonstrate greater compatibility with human organs and tissues. The effect of size, shape, and the method employed for synthesis on the applications in biological systems has been explored by many researchers. This review is a discussion of various synthesis methods employed for their preparation and highlights their applications in biomedical field such as in the treatment of fungal, bacterial, and parasitic infections, cancer, and diabetes. They can also act as chemopreventive agents, anti-inflammatory agents, and as antioxidants. Keywords: Selenium nanoparticles, Chemical reduction , Hydrothermal, Microwave, Biogenic reduction, Biomedical applications. 1. Introduction Elemental selenium (Se) has great importance in the field of physics, chemistry, and biology. Naturally, selenium exists in two forms: inorganic (selenite and selenate) and organic (selenomethionine and selenocysteine). Selenium is found in the form of both crystalline and amorphous polymorphic structures in nature. Monoclinic and trigonal selenium are the crystalline forms. Monoclinic selenium (m-Se) is red in Figure 1: General representation of crystal structure of (a) t-Se and (b) m-Se. appearance and contains rings of Se8. Based on different Reproduced from Ref. 2 with permission from Royal Society of Chemistry, packing, it exists in three allotropic forms (α, β and γ). The copyright 2015. trigonal selenium (t-Se) is black in colour and the most stable usefulness and toxicity is very slender. The United Kingdom crystalline form at room temperature. The Red amorphous (a- group of vitamins and minerals recommended daily intake of Se), Black amorphous and vitreous selenium are the non- selenium by women and men should be 60 µg and 70 µg, crystalline forms of selenium 1. The crystal structures of t-Se and respectively 3. A daily intake of more than 400 µg could be toxic m-Se are represented in Figure 1(a) and 1(b) 2. Selenium, a part which leads to a disorder known as selenosis 3–5. Selenium plays of selenoproteins and selenocompounds within human body a key role in biochemical component of glutathione peroxidase, plays critical role in reproduction, DNA synthesis, thyroid an enzyme responsible for the protection of essential SH-groups hormone, metabolism, and protection form infection and and for the decomposition of peroxides, thereby act as an oxidative damage. It has many industrial and commercial antioxidant. The bactericidal activity of Selenium is because of applications. Due to its high photoconductivity and low melting its capacity to catalyse the oxidation of intracellular thiols, point, it possesses great catalytic activity towards organic causing demise of microscopic organisms 6–8. Selenium, as one hydration and oxidation reactions. Selenium is an essential of the fundamental minor components, is affirmed to improve trace element in the human body but the margin between its the action or restore the activity of the seleno-catalyst and glutathione peroxidase in prevention of free radical harm to cells and tissues in vivo 9–12. It is widely utilized in nutritional a. NanoChemistry and Quantum Dots R & D Laboratory, Department of Applied Chemistry, Defence Institute of Advanced Technology (DIAT), Ministry of Defence, supplements as well as a potential nutrient in fertilizers 13. A Govt. of India, Girinagar, Pune-411025, India. selenium free diet leads to malfunctioning of the liver and * Corresponding author Email: pawankhanna2002@yahoo.co.in hemolytic processes. Se deficiency leads many diseases such as See DOI: 10.1039/x0xx00000x Please do not adjust margins
PleaseMaterials do not adjust margins Advances Page 2 of 17 ARTICLE Journal Name Kashin-beck disease 14, neurological disorders 15, chronic applications in biomedical area because of excellent View Article Online degenerative diseases 16. Selenium supplements can prevent antibacterial activity, sometime, even more effective than Ag DOI: 10.1039/D1MA00639H diseases, such as viral infections 17, immune system dysfunction NPs 40–42. SeNPs have been synthesized in various forms such as 18, and neural function loss 19. The recent boom in nanowires, nanorods, nanotubes through various methods such nanotechnology furnished indefinite number of applications of as sonochemical 43, refluxing, microwave 44, hydrothermal 45, metal nanoparticles in biomedicine. Metal NPs of Au, Ag gamma irradiation 46, pulsed laser ablation 13,47,48, and physical however, have immense medicinal benefits but are costlier to evaporation approaches 49–51. The precursors mostly used in synthesize, however, Se nanoparticles (SeNPs) synthesis is these methods are sodium selenite, sodium selenate, sodium This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. economical and they can be integrated with other biological selenosulphate, selenous acid and selenium oxide. Use of these agents to enhance their biological properties. Vahdati et al. 20 precursors is often preferred because selenium in selenite and Materials Advances Accepted Manuscript demonstrated the synergistic antimicrobial effect of SeNPs and selenate form possesses hazardous effect even at extremely lysozyme. Due to higher surface-to-volume ratio at the nano- low concentrations and gets accumulated in the bio-system. In level, the surface of the particles is more exposed which lead to recent times Khanna et al. have demonstrated exclusive use of Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. the enhanced activity of selenium more profoundly in the nano- 1,2,3-selenadiazole as a source of selenium for variety of regime. The promising potency of SeNPs in biological semiconductor NPs ink/quantum dots including selenium applications are as: an antioxidant, cancer therapeutic agent, nanoparticles 2,52–55. Converting them to biologically and and drug carrier 21. Several studies have supported the technologically important SeNPs can help in revitalizing anticancer 22, antioxidant 21, antimicrobial 23–25, and anti-biofilm environment and protect from contamination of Se properties 26. Use of nano-Se medication in the therapy of compounds. Various reviews on biological applications of huntington’s disease has given promising results 27. SeNPs selenium nanoparticles and its compounds 56 have been possess unique semiconducting, photoelectric and X-ray- published in the recent years while focusing on their biological sensing properties, and are used in photocells, photocopying, synthesis methods 57. This review emphasizes on the different photometers, xerography 28. Their importance in renewable synthesis methods of SeNPs and their advantages and energy devices has also been greatly mentioned 29. Additionally, disadvantages over each other. The authors also presented a Selenium nanoparticles (SeNPs) are environmentally important detailed discussion of various biological applications of SeNPs because of their mercury capturing properties 30. such as anti-cancerous, antioxidative, antidiabatic, The absorption profile of selenium indicated that the nano- antiparasitic, antimicrobial, antibacterial, antifungal and as selenium can lead to blue shift in absorption spectrum and the chemopreventive agents. range of such shift can vary from preparation to preparation. Thus, it is gathered that the bandgap of Se increases from 1.7 eV in bulk to 3.3 eV in the nano-range 31. The least toxic form of 2. Synthesis Methods selenium is elemental Se, hence, their nano form has attracted SeNPs synthesis is reported by many methods. These methods significant attention. Interestingly, functionalized SeNPs exhibit can be broadly divided into two categories namely biological less cytotoxicity than their other forms such as selenate, and chemical reduction. Biological reduction method includes selenite, selenoproteins, and inorganic selenium 32,33. In clinical reduction of various organic/inorganic compounds of selenium, trials, instead of conventional selenium sources, the elemental via biological agents such as bacteria or plant extracts and nano-sized selenium can be better replacement. Figure 2 converts them to non-toxic and beneficial SeNPs. Chemical demonstrates the reduced cytotoxicity as selenium reduction uses chemical reducing agents. This method can nanoparticle size increases 34. SeNPs are highly biologically further be classified depending upon the energy source used or active 35, anti-hydroxyl radical 36, chemo-preventive 32,37, have the apparatus employed for the reaction. Researchers have detoxifying effect on heavy metal exposure 38, and prevents reported mainly hydrothermal, microwave, and sonochemical DNA oxidation 39. method in this category. This broad classification is represented in Figure 3 and then these methods are further discussed in sub- It has been demonstrated by various researchers that impetus sections. on research in SeNPs is greatly desired, owing to its tremendous 2.1. Chemical Reduction Method Among the vast varieties of synthesis methods reported, reduction of Se salts is the most common and simplest method to synthesize SeNPs 58. The sources can be natural compounds from plants or microorganisms 59,60 or reagents/chemicals having ability to cause reduction in oxidation state such as ascorbic acid 61. However, the nanoparticles (NPs) synthesized from natural compounds are found to be less toxic than those prepared by employing chemicals 62. In this section, synthesis Figure 2: Extent of cytotoxicity from various sources of selenium with respect to their size. Reproduced from Ref. 34 with permission from Science Elsevier, copyright 2017. 2 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins
Page 3 of 17 PleaseMaterials do not adjust margins Advances Journal Name ARTICLE by using PVA or chitosan. Likewise, Shah et al. 68 also usedOnline View Article PVA as the stabilizer to obtain SeNPs of size 50-100 nm. The authors DOI: 10.1039/D1MA00639H for the first time reported that sodium selenosulphate responded to acrylonitrile monomer, forming SeNPs. By replacing acrylonitrile with acetonitrile, the authors could not isolate Se nanoparticles. This suggests that the nitrile group was not directly involved in the reaction. Using hyperbranched polysaccharide as stabiliser in reaction of selenious acid with This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. ascorbic acid in water led to formation of highly stable (>1 month) SeNPs of average size about 24 nm which was Materials Advances Accepted Manuscript calculated through DSC 69. Lin et al. 70 used a very mild reducing agent i.e., dilute SO2 solution and selenious acid as the selenium Figure 3: A systematic representation of various synthesis methods of selenium source. Selenous acid being a strong oxidising agent gets easily nanoparticles. Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. reduced by SO2. Sodium dodecyl sulfate (SDS) was used as via chemical method is discussed and synthesis from natural stabilizer and reaction temperature was kept 80oC. The compounds i.e., biogenic reduction will be discussed in later variation in particle size with time was studied by TEM. The section. Chemical reduction uses chemical compounds that particle size varied from 30 nm to 200 nm in a time span of 30 reduces the element, its salt or compounds and controlling the sec to 4 minutes. The article by Yu et al. 71 highlighted the use size by use of surfactants or growth terminating reagents such of sodium thiosulfate as the reducing agent. Reaction of as polyvinylchloride (PVP), folic acid etc 63 to get stable colloidal selenium dioxide with sodium thiosulfate in presence of SDS for solution of SeNPs desired for various applications. Taking SeO2 about 4 hr in ambient conditions yielded monodispersed SeNPs as the precursor, El-ghazaly et al. 64 synthesized spherical SeNPs of about 70 nm in size as estimated from the TEM images. about 13 nm in size where PVP served as the stabilising agents Huang et al. 72 studied the effect of SeNPs size on their inhibiting and KBH4 as the reducing agent in ice-cold solution. The action towards methicillin sensitive and methicillin-resistant appearance of orange colour indicated formation of α-Se. The Staphylococcus Aureus (MSSA and MRSA). For this, they particle shape and size was
PleaseMaterials do not adjust margins Advances Page 4 of 17 ARTICLE Journal Name red Se showed trigonal structure as deduced from the XRD were synthesized via reduction of Na2SeO3 via View hydrazine Article Online measurements where the peaks are observed at 2θ 23.92o, Chloride. The XRD peaks (Figure 4 b) at 2θ 2310.1039/D1MA00639H DOI: ο, 28ο, 42ο, 46ο and 30.11o, 41.64o, 44.16o, 45.89o, 52.31o, 56.31o, 56.55o and 52ο confirmed the formation of black Se in tri-dimensional 62.07o. For the black monoclinic Se, peaks were obtained at 2θ phase 78. Glucose and Na2SeO3 were sealed in an autoclave and 21.80o, 24.80o, 33.19o, 43.51o, 46.79o and 62.70o. Hence, by reacted in ethylene glycol and water mixture at 85 oC for 45 simply varying the reaction time, various polymorphic form of minutes. From this reaction, Chen et al. 79 obtained t-Se Se can be achieved 2. In another report, SeCl4 was taken as the spherical nanoparticles of 320 nm average size which further source and was reduced using hydrazine. They used polymer converted into nanorods on prolonged reaction. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. SDS as the surfactant and exposed to microwave radiation for 4-5 minutes at 750 W to obtain black SeNPs. Several researchers 2.2. Biogenic Reduction Materials Advances Accepted Manuscript have used the microwave irradiation to synthesize SeNPs with Green synthesis of metal NPs have gained researchers’ narrow size distribution 74. Mellinas et al. 75 for the first time attention in the last two decades. Despite the various reported the use of Theobroma cacao L. bean shells (CBS) as the advantages of SeNPs over organic and inorganic selenium Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. reducing and stabilising agent for synthesis of SeNPs. The compounds, the main problem is its poor cellular intake. authors have designed a model using central composite design Therefore, it is desirable to synthesize SeNPs via biological route technique to optimize the reaction condition. The data for 23 to offer improved bio-compatibility and stability. The previous different sample was fed which included parameters such as methods mentioned above require chemical reducing and time, power, amount of precursor i.e., Na2SeO3, Z-potential and stabilising agents which may be toxic and can hinder their crystallite size. Based on this model, the optimal reaction utilization in biological systems. Generally, it is believed that conditions came out to be 15.6 min, 788.6 W and 0.14 g of biological agents from plant extracts and microorganisms Na2SeO3 and 50 ml CBS extract solution which yielded particles address a superior option in contrast to chemical methods to of diameter ~ 42 nm. The TEM images revealed uniformly satisfy the developing interest for low-cost and non-hazardous distributed spherical particles of 1-3 nm in diameter which they preparations. It is reported that biological extracts act as bio- found stable for 2 months. The attempt opens up the detailed reducing agents, as well as stabilizers for nanoparticles. There is study of SeNPs in a microwave and also highlights the tremendous amount of literature available on the biosynthesis technological applications of SeNPs in food and medicine. of SeNPs 80–87. The biological agent mediated synthesis is easy Whereas, Panahi-Kalamuei et al. 31 reported SeNPs using as this does not require special apparatus and conditions. These chemical compounds such as sodium dodecyl sulfate (SDS), biological reagents include bacteria, fungi, algae, protein polyethylene glycol (PEG 600) and cetyltrimethylammonium molecules and plant extracts. Such as, several researchers have bromide (CTAB). SeCl4 was used as the starting material which reported SeNPs using fenugreek extract 88, Cassia auriculata on dissolving in water produces selenious acid which was extract 89, E. officinalis fruit extract 90, microbial polymers 91, reduced using hydrazine hydrate. The reduction potential of Bacillus sp. B2 92, Saccharomyces cerevisiae var. boulardii yeast Se4+/Se is 0.74 eV and that of N2H4.H2O/N2 is -1.16 eV Hence, cells 93, Penicillium chrysogenum 94, Penicillium expansum 95, the electrode potential 1.9 eV. Therefore, they chose hydrazine Vitis vinifera aq. 96, Withania somnifera extract 97, Azadirachta hydrate as the reducing agent and microwaved the mixture for indica 98, Aloe vera leaf extract 99, Burkholderia fungorum 100, 4 min at 750 W to obtain 5-25 nm particles using SDS. They Diospyros montana leaf extract 101, lemon leaf extract 102, or mentioned that when surfactant like CTAB and PEG were used bacteria grown from Mueller-Hinton broth 103 as reducing bigger sized and agglomerated particles were formed. agents and incubating the precursor mixture for a day or two. According to them, this was because Se4+ ions present in the However, use of plant extracts is even more cost effective than reaction media are more stabilised by anionic surfactant. using bacteria or fungi as bacteria culture and isolation requires Similar, trend was observed on increasing/decreasing reaction technique, experience, and special equipment. With this time/wattage. method, high-quality SeNPs can be produced without requiring specific equipment, with less or no product wastage, and 2.1.2. Hydrothermal Method without large amount of solvents. Hence, such methods are Hydrothermal method is not widely popular for the synthesis of considered as single step, inexpensive and eco-friendly. The biologically compatible SeNPs as reflected from the scarcity of plant extracts contain terpenes, flavonoids, tannins, coumarin, literature. However, the reports which are available showed cinnamic acid, phenolic acid, vitamins, sterols, polysaccharides, that very small sized particles 10-20 nm can be achieved by this enzymes, proteins etc. which can act both as reducing and method. Shin et al. 76 reported the use of cellulose nanocrystals stabilizing agents. Recently, a few review articles brought out for the first time in reduction of Na2SeO3 to obtain SeNPs having the importance of plant-based SeNPs, the simplicity in the size range 10-20 nm. The method is very convenient and eco- synthesis and the feasibility for biological applications 57,104. friendly. Another example of the environment-friendly Moreover, SeNPs preparation using medicinal plants may synthesis is the synthesis reported by Abbasian et al. 77 where enhance their beneficial properties. These biological catalysts they used coffee bean extract to reduce Na2SeO3 to form Se. are vital environmentally, as they reduce the toxic oxyanions The reaction completed in 15 minutes and at medium present in the environment into non-toxic elemental selenium. temperature. Spherical nanoparticles of average size ~15 nm Figure 4 b shows the XRD pattern of SeNPs synthesized using 4 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins
Page 5 of 17 PleaseMaterials do not adjust margins Advances Journal Name ARTICLE drumstick extract showing peaks at 2θ 25.38o, 29.98o, 46.1o, 161.5 eV for Se 3d5/2 and Se 3P3/2 affirms Se in the zero-valent View Article Online 53.00o, 62.38o, and 72.00o due to [100], [101], [111], [201], state. The XPS spectra is shown in FigureDOI: 4 d 10.1039/D1MA00639H 109. [103], and [113] planes showing crystalline nature of Se 105. In another report, Ramamurthy et al. 88 prepared 100-150 nm However, the XRD diffraction peaks for red Se prepared from SeNPs both by chemical and biogenic method. They observed Muller-Hinton broth were obtained at 23.78o, 29.79o, 43.88o that the size obtained from biogenic method was slightly bigger indexed to the face centred cubic (fcc) planes [100], [101], from that prepared by chemical method, yet biogenic method [102], respectively and UV absorption was observed at 263 nm proved to be more efficient mainly because biological strains 103. While, the most intense peak for hexagonal phase of SeNPs are a combination of various reducing and stabilising agents. For This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. appears at 29.73ο 106. The Characteristic Raman peak for the synthesis of SeNPs, researchers have mostly reported the elemental Se is observed at 254 cm-1. However, slight shifting use of biogenic/biotic reduction. The various biological agents Materials Advances Accepted Manuscript may be observed depending upon the polymorphic forms of Se. used along with the precursor and reaction conditions are Figure 4 c shows the Raman spectra of SeNPs synthesized via summarized in Table 1. laser ablation method which shows mixture of various phases Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. 48. The authors interpreted that the peak at lowest frequency 131 cm−1 corresponds to bending vibrations. The Se-Se 3. Biomedical Applications stretching in crystalline Se chains appear at 237 cm−1 and 250 Biomedical applications of SeNPs have attracted global interest cm−1. The 259 cm−1 peak was reported due to the vibration of many researchers due to their importance at cellular and modes of in Se8 crown structure. In general, depending upon tissue levels. It is well known that excessive production of toxic the intensity of particular peak, one can estimate about the type reactive oxygen species (ROS) can be triggered by various of Se formed. Piacenza et al. 107 suggested the use of biologically abiotic stresses, thus triggering generation of several diseases, synthesized SeNPs in bio-imaging. They synthesized SeNPs from due to damaged essential nutrients such as carbohydrates, yeast extract which exhibited strong photoluminescence proteins, and lipids 110. The continuous rise in disease like emission in blue-red region of the visible spectrum and cancer, diabetes, bacterial infections have threatened luminescence lifetime comparable to mostly used fluorophores. worldwide healthcare system. Currently, treatment of cancer Afzal et al. 108 reported the use of various cyanobacterial strains needs various kinds of therapies such as chemotherapy, for the biogenic synthesis of SeNPs and studied their radiotherapy, or combination of both to tackle global death rate antioxidant properties. Out of the many strains used, 111,112. The adverse effect of such therapies generally is of great Arthrospira indica SOSA-4 was suggested to be the best strain concern 113. It has been documented that Se supplements as it yielded SeNPs of 11.8 nm and improved antioxidant alongside regular anticancer treatments upgraded the activity. When heated for few minutes, reaction of L-cystine productivity of chemotherapeutic medications, declining with selenious acid yielded cystine capped SeNPs whose size results and enhancing generic state of the patients 114–116. The was determined by DLS technique and valency was confirmed new clinical preliminaries have assessed well-being and by the XPS spectra. The appearance of peaks at 55.5 eV and efficiency of selenium, both in viability and poisonousness of normal anticancer treatments 117. Numerous in-vivo and in-vitro studies at supranutritional level have exhibited an anticancerous impact by selenium 118,119. Davis et al. 120 reported that frequency of liver malignancy can be decreased by 35 % on consuming supplements of selenite salt. Few studies revealed that by taking 200 µg of selenium each day, as Se yeasts, danger of colorectal, lung, and prostate cancers have decreases 121. Similarly, Se supplements also reduce the stomach malignancy danger 122. It has also been examined that lower degree of selonoprotein (SelP) causes more danger to prostate, throat, kidney, colon, and cellular breakdowns in the lungs 123. Selenium rich Brassica and Allium plants lessen the danger of colon malignant growth 121. Despite of having such advantages these organic and inorganic sources of selenium possesses higher toxicity and lower biocompatibility. To overcome these issues, SeNPs came to the limelight. Nano- Figure 4: (a) XRD pattern of SeNPs synthesized via hydrothermal method. Reproduced selenium in the form of nano-medicine offers excellent from Ref. 78 with permission from Science Elsevier, copyright 2013, (b) XRD pattern of properties such as antimicrobial, anticancer, antidiabatic, SeNPs synthesized using drumstick extract. Reproduced from Ref. 105 with permission antiparasitic, and antioxidant as shown in Figure 5. The from John Wiley and Sons, copyright 2019, (c) Raman Spectra of Se representing antioxidative property of nano-selenium minimizes the impact presence of various phases at different energies. Reproduced from Ref. 48 with of ROS and free radicals. The higher efficiency of SeNPs shows permission from Springer Nature, Copyright 2019. And (d) XPS Spectrum of L-Cysteine capped SeNPs. Reproduced from Ref. 109 with permission from RSC Publications, augmented medicinal effects such as antibiotics, antidiabetic, copyright 2017. cytotoxic chemoprotective medicines in comparison to the traditional therapeutic medicines 138. These can also be used as This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 5 Please do not adjust margins
PleaseMaterials do not adjust margins Advances Page 6 of 17 ARTICLE Journal Name View Article Online DOI: 10.1039/D1MA00639H Table 1. Summary of reactions carried out by various researchers for synthesizing SeNPs using different biological sources. Biological Reaction Morphology and Size of S.N. Se Precursor Applications Ref. Agent/Extract Origin Conditions Particles Spherical with diameter 10- This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Antimicrobial Incubated at 50 nm, λabs = 263 nm, 1. SeO2 Bacillus licheniformis against foodborne 103 37oC for 48 h. Colourless to orange-red pathogens Materials Advances Accepted Manuscript (Red Se) Chemopreventive Incubated at Spherical with diameter 50- 2. SeO2 Bacillus licheniformis against lung 124 Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. 37oC for 24 h. 80 nm, λabs = 560 nm carcinoma Antibacterial against Incubated for λabs = 560 nm, Size ~ 153 nm gram positive and 3. Na2SeO3 Azadirachta Indica 5 min and λabs = 580, 670 nm, Size ~ 287 98 gram negative 10 min nm bacteria Stirring at Trigonella D=20 nm, Nanospheres with Anticancer room 4. SeO2 foenumgraecum leaf 5-12 nm diameter, λabs = 355 Degradation of 125 temperature extract nm sunset yellow FCF for 2-8 h. Terminalia Incubated at Size = 10-80 nm, λabs = 390 Effect against As(III) 5. Na2SeO3 126 Arjuna leaf extract 30oC for 72 h. nm, Dark red, λem = 595 nm toxicity Interaction with Heating at 6. H2SeO4 L-Cystine Nanospheres ~60 nm, Red Se human serum 109 105oC for 1 h. albumin Absorption band = 200-400 Trigonella foenum- Incubated at 7. H2SeO3 nm, Red Se, 50-150 nm oval Breast Cancer 88 graecum L leaf extract RT for 24 h. particles Instant Prevention of PVC 8. Na2SeO3 Glutathione (GSH) formation of Nanospheres 40-100 nm related medical 127,128 SeNPs infections Instant Cytoxicity of SeNPs formation of Hemispherical, size = 80-200 9. Na2SeO3 Glutathione (GSH) coated PVC in rat 6 SeNPs in basic nm dermal fibroblasts media λabs = 280 nm , Raman = 254 Na2SeO3.5H2O, Pseudomonas Incubated for Explain role of PVP 10. cm-1 (m-Se), Nanospheres 129 Capped with PVP alcaliphila (bacteria) 48 h. in text 40-100 nm Refluxed together for 11. H2SeO3 Vitis vinifera extract Nanospheres 3-18 nm ---- 130 15 mins in water Ethanol extract of Bee Brown to orange colour Antioxidant, propolis from Apis Stirred at RT change Antimicrobial, 12. Na2SeO3 mellifera colonies 131 for 24 h λabs = 265 nm Antibacterial, along with Ascorbic 52-118 nm diameter Antifungal Acid 7-45 nm, Stable upto 2 Incubated for months 13. Na2SeO3 Allium sativum extract 72 h until Antioxidant 132 Dark pink colour of solution, color change λabs = 400 nm 14. SeO2 Lactobacillus bervis Incubated at ---- Anticancer 133,134 6 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins
Page 7 of 17 PleaseMaterials do not adjust margins Advances Journal Name ARTICLE 37oC for 72 h (Studies on mice View Article Online with breast cancer) DOI: 10.1039/D1MA00639H λabs = 259-274 nm, Red Incubated at Various cyanobacterial spherical NPs with sizes in 15. Na2SeO3 32oC for 2-5 Antioxidant 108 strains the range 11-60 nm days depending upon the strain λabs = 299, 400 nm, λem = 599 nm, Bandgap = 2.3 eV Degradation of This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Mixture of nanospheres and sunset yellow dye Moringa oleifera Incubated at nanorods Anticancer studies 16. Na2SeO3 (Drumstick) leaf 105 RT for 24 h Average size = 18.85 nm on human colon, Materials Advances Accepted Manuscript extracts (calculated by scherrer breast and hepatic equation) and 23-35 nm cancers from TEM Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. Orange-Red Se Kept λabs = 270 nm Crispum (Parsley) leaf overnight at Spherical with maximum 17. NaHSeO3 ------ 135 extracts room number of particles around temperature Size = 400 nm (DLS) Zeta potential = -14.2 mV Rhizobacterium Nanospheres of 50-100 nm Incubated at 18. Na2SeO3 Azospirillum brasilense in diameter coated with thin --- 136 32oC for 24 h Sp7 layer of protein Protection against L-Cystine and peptone Stirring for 10 36.2 nm (from XRD) 19. Na2SeO3 irradiation used 106 from soyabean h at 25oC 20-50 nm (TEM) nephropathy Antibacterial against gram (+), gram (-) Diospyros montana Incubated at 20. H2SeO3 4 -16 nm from TEM and DLS bacteria and fungi, 101 leaf extract RT for 24 h Anticancer against human breast cancer Mushroom polysaccharides 100 to 600 nm in size Kept at RT for Anticancer study protein complex – depending upon 21. Na2SeO3 12 h with against human 137 Stabilising agent, concentration of stabilising stirring breast cancer cells Ascorbic acid – agent Reducing agent therapeutic and theranostic agents 139. It is noteworthy that Based on above mentioned advantages the next section various studies on SeNPs evidenced reduced toxicity and discusses the various applications of SeNPs in detail. characteristics of interfacing biomaterials with tissue and cell. SeNPs are biologically active and naturally accessible which takes part in numerous oxidoreductive cycles. They also show many regulative outcome to help the appropriate working of plant and living bodies and numerous medical advantages 34,140,141. Researchers have shown that SeNPs can be utilized as a cancer preventive agent by controlling the cell damage aroused due to free radicals, anticancer therapies, and antimicrobial agents. These can also be used as an ingredient in nano-biosensors fabrication. The action mechanism of SeNPs can be defined in two ways: (a) by generation of ROS or disrupting the integrity of cell membrane, (b) altering the DNA sequence of microorganism by damaging the cell wall and binding to the cell membrane to inhibit the growth of microorganism. The cycles associated with SeNPs preparation can be utilized in wastewater treatment and bioremediation. It can play significant role in the treatment of heavy metals by Figure 5: Pictorial representation of various applications of selenium combining with them to supress their poisonous impact 56. nanoparticles. 3.1. Anti-carcinogenic Activity This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 7 Please do not adjust margins
PleaseMaterials do not adjust margins Advances Page 8 of 17 ARTICLE Journal Name Nowadays, selenium nanoparticles are widely being which increases interferon generation and delayed View Article Online investigated in anti-cancer activities against breast, lung, hypersensitivity for triggering immune response 134. Therefore, DOI: 10.1039/D1MA00639H kidney, and osteosarcoma based on in-vivo and in-vitro it is reported by many researchers that if SeNPs are conjugated experiments 88,124,134,142,143. However, due to selenium toxicity with organic moieties and drug, they can inhibit accumulation and bioavailability in the form of elemental selenium and of Se nanoparticles, thereby enhancing anticancer activity, and naturally sourced selenium (selenocysteine and minimizing antibiotics toxic effect 88,143,152–155. The nano- selenomethionine) cannot be used in cancer therapies 144. The conjugates of SeNPs and doxorubicin show enhanced cytotoxic nano-selenium has advantages over other natural sources of effect against cancer cell by assisting the antibiotic cellular This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. selenium because of its size, porosity, and bio-dispersion. Thus, uptake. In a study of lactate dehydrogenase activity and cell the polyporus umbrellatus polysaccharide (PUP) capped SeNPs viability, Yang et al. 143 found that doxorubicin alone was Materials Advances Accepted Manuscript have been utilized to detect in-vitro anti-proliferation effect responsible for destroying 20 % of cancer cells whereas more with MTT assay. Particularly, PUP-SeNPs inhibit cell growth of than 50 % of cancer cells destroyed by conjugation of SeNPs four types of human cancer (a) cell MDA-MB-23 causing breast and doxorubicin. cis-platin an anticancer drug responsible for Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. cancer in human, (b) HepG2 cells responsible for human liver oxidative stress and DNA cross-linking leads to nephrotoxicity cancer, (c) Hela cells known for human cervical cancer, (d) HT and spermatotoxicity. Interestingly, nephrotoxicity can be 29 for colon cancer. It is shown by the researchers that by using reduced using 11-mercapto-1-undecanol functionalized SeNPs nano-selenium of above nature, no toxicity to normal human by preventing ROS-mediated apoptosis. The antioxidative cells such as liver cell (LO2), embryonic kidney cell (293T), and property of SeNPs in combination with cis-platin enhances the mouse embryonic fibroblast cell (NIH3T3) was observed 145. A sperms quality and spermatogenesis 153,154. During the breast schematic of effect of SeNPs on cancerous and normal cell is cancer treatment, anastrozole is used to inhibit the growth of shown in Figure 6 146. aromatase which leads to side effects such as bone fracture and osteoporosis. These toxicities can be prevented by conjugating anastrozole with SeNPs 155,156. Similarly, SeNPs prepared using highly branched β-(1-3)-D-glucan obtained from fruiting plants of auricularia auricular-judae (AF1-Se) showed strong suppression against human breast adenocarcinoma cancer cell lines such as MCF-7, MDA-MB-468, and MDAMB-231 157. SeNPs decorated using various polysaccharides extracted from pleurotus tuberregium (PTR), ganoderma lucidum (GL), coriolus versicolor (CV), and polyporus rhinoceros (PR) showed highest activity for gastric cancer cell lines AGS 158. Induction of cell apoptosis is the key mechanisms that plays important role in antitumor activities of SeNPs and polysaccharides conjugates. Apoptosis, which is also known as programed cell death, can be described by certain governing properties such as nuclear chromatin condensation, cytoplasm shrinkage, development of apoptotic parts, and membrane dysfunction 159. The cellular growth of human lung cancer cell A549 can be inhibited by Figure 6: A schematic of effect of SeNPs on Cancerous and normal cell. Reproduced from Ref. 146 (A. Khurana, S. Tekula, M. A. Saifi, P. Venkatesh and C. Godugu, utilizing complex of arabinogalactans (LAG) and SeNPs 160. The Biomed. Pharmacother., 2019, 111, 802–812), copyright authors 2019, open human breast cancer cell can be treated by PUP coated SeNPs access Science Elsevier. through stimulating mitochondria mediated and death receptor mediated apoptotic pathways. The anti-cancer activity of these It has been demonstrated by numerous analysts that complexes regulated by Bax/Bcl-2 ratio, endorsing cytochrome incorporation of low Se leads to various hazardous diseases. Se -c release, enhanced caspase-9,-8, and -3 activities and poly act as a chemopreventive agent when utilized at optimal doses (ADP-ribose) polymerase cleavage 161. Therefore, the higher 147,148. Selenium therefore has been proposed as a disease toxicity of SeNPs for cancer cells can be synergistically utilized therapy agent in combination with chemotherapy and radiation with anticancer drugs in the cancer treatment. 117. The most extreme anticarcinogenic effect of Se has been reported to be when it is administered at beginning phase of the disease 149,150. The risk of cancer in human can increase due 3.2. Antioxidative Activity to presence of arsenic (As) in drinking water. However, it is ROS and reactive nitrogen species (RNS), (the free radicals) are reported that the generation of As(III)-activated ROS can be generally generated in human body during several physicochemical minimized by use of terminali arjuna (TA) leaf extract and biochemical reactions. The higher amount of intermediate encapsulated SeNPs, which fortifies As(III)-induced cell death complexes such as superoxide and hydrogen peroxide produced and DNA catastrophe 102,151. The metastatic breast cancer in a during these reactions are responsible for cellular damage, leading mice model is reported to be affected when treated by to generation of lethal diseases. Therefore, antioxidative compounds administering oral dose of Lactobacillus brevis with SeNPs, are utilized to suppress the creation as well as scavenging of these 8 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins
Page 9 of 17 PleaseMaterials do not adjust margins Advances Journal Name ARTICLE free radicals 162,163. The surface of Se nanoparticles decorated with plant based SeNPs shows better prevention against ROS mediated View Article Online various organic molecules and plant extracts act as both antioxidants oxidative stress induced diseases. DOI: 10.1039/D1MA00639H and pro-oxidants on different cells of human body and their action mechanism is shown in Figure 7 164. Battin et al. 165 reported that 3.3. Antidiabetic Activity selenium nanoparticles can play an important role in minimizing the free radical's concentration to protect oxidative damage of DNA in The high amount of glucose in our body due to absence of both in-vivo and in-vitro experimental conditions. It is also enough insulin creation or inadequate usage of insulin, leads to documented that, selenoprotein is a key source of selenium, chronic disease like diabetes. The insulin chemical is responsible This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. produces vital antioxidants such as deiodinase, thioredoxin for maintaining the blood sugar level. Diabetes negatively reductase, and glutathione peroxidase 166. In an investigation, Zhang impacts people of all age groups. Several researchers have reported the use of selenium nanoparticles in the treatment of Materials Advances Accepted Manuscript et al. 167 showed that sodium selenium inhibited the growth of Candida utilis by improving the excretion and biosynthesis of diabetes because of its effective controlling ability to regulate glutathione. Similarly, chitosan functionalized SeNPs showed blood sugar level 171. The long term effects of diabetes can damage large and small blood vessels, causing problem in Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. enhanced glutathione peroxidase and anticipated lipofuscin development in mice 168. Additionally, ABTSº+ and superoxide anion functioning of various human organs. Diabetes leads to the radical can be scavenged by utilizing SeNPs in combination with generation of various diseases in heart, legs, brain, eyes, cordyceps sinensis exopolysaccharide 145. The plant-based synthesis kidneys, skin, digestive system, oral health, and immune system of selenium nanoparticles demonstrated antioxidative activity as shown in Figure 8. Deng et al. 172 reported that Se through ABTS and DPPH assay 169. Further, Kong and group170 nanoparticles loaded with insulin (INS-SeNPs) can be delivered presented enhanced antioxidative activity of gum-arabic orally to treat diabetics in mice. In their study the researchers functionalized SeNPs (GA-SeNPs) for scavenging hydroxyl radicals stated that the insulin was released in blood in a controllable and DPPH assay test. In an investigation, selenium nanoparticles manner and showed excellent stability in digestive foods. Liu indicated hepatoprotective component against acetaminophen and group 173 examined enhanced antidiabetic activity of accelerated hepatotoxicity by refining liver capacity and restraining catathelesma ventricosum polysaccharides (CVPs) coated Se oxidative stress in rats. In another study Kokila et al. 101 nanoparticles in streptozocin (STZ) induced diabetic mice. demonstrated conceivable antioxidative property of SeNPs It is Similarly, effect of SeNPs in combination with insulin was gathered from the literature that shape and size of nanoparticles can investigated by Quraishy et al. 174 to enhance the activity of play key role in such studies. For example, hollow spherical selenium hyperglycemia and hyperlipidemia in STZ induced diabetics in nanoparticles have shown antioxidative properties 32,36,37. Thus, mice. At a concentration of 2.0 mg/Kg body weight, chitosan stabilized SeNPs resulted in improved antidiabetic activity 175. Furthermore, phytomedicines are proven candidates to combat diabetes in an effective way 176. Therefore, Deng et al. 177 demonstrated that extracts of mulberry leaf and pueraria lobata (MPE) (phytomedicines) coated SeNPs having hypoglycemic effect can cure diabetes mellitus. The plasma associated selenium demonstrated positive effect on prevalent and incident diabetics by redox regulation and signaling of Figure 7: A systematic representation of action mechanism by surface decorated Se NPs on various cells as an antioxidant and pro-oxidant. Reproduced from Ref. 164 with Figure 8: Effect of diabetes on various human organs. permission from Science Elsevier, copyright 2020. This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 9 Please do not adjust margins
PleaseMaterials do not adjust margins Advances Page 10 of 17 ARTICLE Journal Name insulin pathways 178. Therefore, selenium nanoparticles proteus mirabilis, (P. mirabilis), and pseudomonas aeruginosa View Article Online functionalized with various moieties are expected to play crucial (P. aeruginosa) to check viability of biogenic SeNPs-Bacillus sp DOI: 10.1039/D1MA00639H role in treating different type of diabetes. A schematic of SeNPs MSh-1, having spherical morphology with dimension range of effect on various diabetic cells is shown in Figure 9 146. 80-220 nm. For comparison purpose they incubated biofilm formation assay with both SeNPs and SeO2 with microbes. In both the cases, they observed no significant decrease in the biofilm formation; however due to lower toxicity of SeNPs they were preferred over SeO2. It was believed that SeNPs shows This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. antibacterial activity due to oxidative stress 185. Huang et al. 186 reported a new inorganic antibacterial agent based on quercetin Materials Advances Accepted Manuscript (Qu) and acetylcholine (Ach) functionalized SeNPs (Qu- Ach@SeNPs), which demonstrated improved antimicrobial activity against multidrug-resistant superbugs (MDRs) in Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. contrast to individual Qu@SeNPs and Ach@SeNPs. They observed that when Qu-Ach@SeNPs adhered to the bacteria cell surface, causing disruption of cytoplasmic membrane, inhibits the growth of bacterial cell methicillin resistant S. aureus (MRSA) and damaging the DNA structure by Figure 9: SeNPs effect on diabetic cells. Reproduced from Ref. 146 (A. Khurana, S. antibacterial action as shown in Figure 10 186. Tekula, M. A. Saifi, P. Venkatesh and C. Godugu, Biomed. Pharmacother., 2019, 111, 802–812), copyright authors 2019, open access Science Elsevier. 3.4. Antimicrobial Activity Living beings are susceptible to microbial infection leading to numerous diseases causing great health concerns. Nowadays, most of the pathogenic organisms have become drug-resistant because of the constant utilization of wide range of antibiotics. Particularly, multidrug-resistant microorganisms and fungi are profoundly becoming irresistible as they have procured protection from practically all the accessible antimicrobial drugs 179–181. Therefore, anti-infection agents are being created for the treatment of these irresistible diseases. There are a variety of Figure 10: A schematic representation of synthesis of Qu-Ach SeNPs and their metal nanoparticles as well as metal oxides and their antibacterial action. Reproduced from Ref. 186 with permission form Science Elsevier, combinations that have been documented as potential copyright 2016. antimicrobial agents. SeNPs have also found tremendous scope in biomedical applications as an antimicrobial agent to protect In a separate study researchers 40 also found that in-vitro study implanted clinical gadgets from bacteria. Tran et al. 41 involving SeNPs emphatically suppressed the growth of S. incorporated SeNPs by in-situ method into regular polymers aureus (60 times higher) at different doses such as 7.8, 15.5, and such as polyvinyl chloride, polyurethane, and silicon, generally 31 µg/mL for a time period of 3, 4, and 5 hr, respectively. used in biomedical devices. They observed that the antibacterial However, this study was found unsuitable in microbiology in performance was directly linked with the concentration of terms of effective antimicrobial agent. Therefore, to overcome selenium as coating material in combination with different these issues Mittal et al. 187 combined selenium and silver polymers. Their findings stated that nano-selenium coated nanoparticles to enhance the antimicrobial activity. Here, Ag- polymers essentially can hinder staphylococcus aureus (S. SeNPs having a size range of 30-35 nm, were synthesized aureus) growth, in contrast to uncoated polymers. Additionally, utilizing bioactive gallic acid and quercetin (QC). The composite they discovered that SeNP-covered PVC shows more prominent of Qu-gallic acid@Ag-SeNPs antimicrobial activity was found to antibacterial limit compared to a commercial Ag-covered PVC be superior to both silver nitrate and sodium selenite against 41. Generally, biofilm development on the surfaces of clinical Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) on agar gadgets by microbes is difficult to treat. Thus, SeNPs act as a plates. They also found comparable results of nanocomposite suppressing agent for biofilm formation 34,182–184. Wang et al. 42 with an antimicrobial agent chloramphenicol for an equivalent reported biogenic SeNPs utilizing bacillus licheniformis JS2 to dose of 50 µg/mL. Here, the authors described the antimicrobial suppress bacterial (S. Aureus) adherence, biofilm development, activity mechanism in two ways: in first assumption, and microcolony formation, to the various polymer surfaces. nanoparticles adherence to the wall of bacteria cell, where These outcomes have possible incentive in application as silver NPs release and destroy the bacteria cell. In second antibacterial covering prostheses against S. aureus and other assumption, interconnectivity of AgNPs with DNA and bacterial clinical gadget against nosocomial infections 183. Shakibaie et al. protein and more activity for sulfur and phosphorus compound 26 studied various biofilm forming microbes such as S. aureus, which leads to destruction of these compounds. Menon et al. 10 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins
Page 11 of 17 PleaseMaterials do not adjust margins Advances Journal Name ARTICLE 188 reported biosynthesized SeNPs from Z. officinale with It was assumed that the reason behind this mechanism is View Article Online spherical morphology and 100-150 nm size range. They selenium's physiological impact on specific DOI:proteins in A. niger. 10.1039/D1MA00639H examined the antimicrobial activity of the SeNPs against five The outcomes may have direct ramifications on dermatitis microbial species such as E. Coli, klebsiella sp., pseudomonas caused by A. niger or C. albicans. These pathogenic micro- sp., S. aureus, and proteus sp. The proteus sp. bacteria growth organisms can regrow on the skin by exposing to SeNPs’ was effectively inhibited by SeNPs on utilizing a concentration environment. Generally, post antifungal effects (PAEs) is a vital of 250 µg/mL. Generally, SeNPs possesses size and pharmacodynamic boundary which helps in setting up concentration dependent impacts against various measurement regimes by demonstrating inhibition of This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. microorganisms 189. Further, selenium and tellurium antimicrobe development, after exposing micro-organism to nanoparticles exhibit antimicrobial activity and destruction of antimicrobial agents for a short period of time 195–197. Materials Advances Accepted Manuscript biofilm formation. These nanoparticles were effective on inhibiting growth of E. coli JM109, pseudomonas aeruginosa 3.6. Antiparasitic Activity PAO1, and S. aureus ATCC 25923 190. Consequently, SeNPs can In the past few years, different research groups have put Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. be utilized as an effective antimicrobial agent in pharmaceutical aggressive efforts on exploring antiparasitic property of applications. selenium nanoparticles 25,198,199. Various types of parasitic diseases and their effect on human organs have been shown in 3.5. Antifungal Activity Figure 12. By in-vivo and in-vitro studies, it was found that SeNPs acquire antifungal properties for various biological biosynthesized SeNPs from bacilus sp. Msh-1 resulted in the applications. To name a few, SeNPs can be used for treatment treatment of leishmania major parasite such as promastigote of fungal infections in immunity compromised patients, and amastigote 25. Similarly, in-vitro experiment of improvement in probiotic concentration, to fabricate antifungal leishmanicidal activity to combat leishmania tropica (L. tropica) and antibacterial cloths for protecting skin from S. aureus and 200 and leishmania infantum (L. infantum) 199 are reported by tinea pedis infection 191 as shown in Figure 11. To prove this, Yip use of bacilus sp Msh-1 functionalized SeNPs. Gel- et al. 192 demonstrated that nano-Se modified with biogenic electrophoresis method has been reported for in-vitro polysaccharides-protein (PSP) complexes collected from investigation of selenium nanoparticles to understand time- pleurotus tuber-regium, deposited on a fabric was effective in dependent decrease in promastigote multiplication due to inhibiting growth of S. Aureus and trichophyton rubrum presence of DNA fragmentation 201. Biosynthesized SeNPs with bacteria. Similarly, Shakibaie et al. 193 examined antifungal a size range of 80-220 nm showed a strong scolicidal activity impacts of bacillus sp. Msh-1 functionalized SeNPs against against parasitic infection (Cystic echinococcus) through an in- aspergillus fumigatus (pulmonary infection) and candida vitro study 202. A comparable time-dependent cytotoxic albicans (skin infection). Shahverdi et al. 24 reported SeNPs outcome was also illustrated against intracellular amastigotes. prepared from klebseilla pneumoniae to treat antifungal A study on male mice (BALB/c) infected with leishmania major infection from malassezia sympodialis, malassezia furfur, and showed a reduced progression in lesion growth by ejaculation asperigillus terreus at a concentration range from 10-260 of SeNPs. Soflaei et al. 199 reported the antileishmanial property µg/mL. Particularly, SeNPs provide antifungal activity for of SeNPs in both promastigotes and amastigotes of L. infantum patients having less immunity against nystatin-immune Candida in contrast with SeO2. The study demonstrated that SeNPs sp. 194 and a more constructive therapy to encounter intrusive aspergillosis in comparison to amphotericin B drug 193. However, conflicting results have been obtained by Kazempour and group on SeNPs prepared from klebseilla pneumoniae. They found that the SeNPs lack in treating post antifungal effect of aspergillus niger (A. niger) and candida albicans (C. albicans) Figure 11: A schematic of utilization of SeNPs against various fungal infections. Figure 12: Types of parasitic diseases which can be treated by SeNPs. and less concentration of Se stimulated the growth of A. niger. showed improved performance and less cytotoxicity than SeO2 This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 11 Please do not adjust margins
PleaseMaterials do not adjust margins Advances Page 12 of 17 ARTICLE Journal Name in a time and dosage dependent antileishmanial activity. In chemoradiotherapy and radiation sensitizer. Generally, to treat View Article Online another study, Mahmoudvand et al. 200 reported that SeNPs cancer cell external radiation therapy hasDOI: been utilized broadly. 10.1039/D1MA00639H with a particular size range were effective in inhibiting the However, these unpredictable radiations can damage adjacent resistance of meglumine antimoniate (MA) and MA-sensitive L. healthy cells. To overcome this unavoidable impact, chemo- tropica in-vitro. Essentially, these outcomes indicated radiotherapy can be utilized with a radioactive seed to deliver suppression of promastigote dependent on the dose, decreased enhanced, efficient and precise radiation. Based on this intramacrophage amastigotes feasibility in the two strains, and concept, Bhattacharjee et al. 205 investigated a combined in-vivo outstanding impact on prophylaxis treatment. Additionally, and in-vitro experiment by utilizing folic acid capped SeNPs (FA- This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. SeNPs exhibited improved antileishmanicidal activity in SeNPs) in conjugation with radioactive 125I seeds to impart conjugation with MA, in contrast to SeNPs or MA alone. 138 enhanced anticancer viability. In comparison with individual Materials Advances Accepted Manuscript Hence, it is concluded that biosynthesized SeNPs with a treatment, the blend of (FA-SeNPs) and 125I seeds demonstrated particular particle size range shows higher resistant against better in-vivo antitumor and lower cytotoxicity in MCF-7 leishmania parasitic diseases. infected mice. Yu et al. 209 reported that Se nanoparticles in Open Access Article. Published on 17 December 2021. Downloaded on 1/10/2022 2:27:23 PM. combination with radiation reduces the damage to nearby 3.7. Other Biological Applications tissues and enhances the carcinogenic cell affectability to Besides the antibacterial properties, SeNPs have also been harmful impacts of illumination on breast cancer cell MCF-7 by utilized as wound dressing materials. Biswas et al. 203 confirmed in-vitro study. Karami et al. 106 reported the radioprotective the antibacterial properties of permeable chitosan/polyvinyl impacts of SeNPs and sodium selenite on gamma radiation (0, alcohol (PVA) (CS) in-situ mediated Se nanorods compared to Ag 2, and 8 Gy) incited nephropathy in mice for 14 days. They nanoparticles (CS-Ag). Both the nanoparticles CS-Se and CS-Ag concurrently treated the mice by administrating SeNPs exhibited antibacterial activity against gram-negative (E. coli), (spherical 20-50 nm) or sodium selenite dose (0.1 mg/kg). After gram-positive (S. aureus), and methicillin-safe S. aureus (MRSA). 48-hour exposure they found that SeNPs were more viable than The slow release of Ag and Se nanoparticles were dependent on sodium selenite on controlling the factors responsible for delivery medium utilized during treatment. From the study it nephropathy. was brought out that CS-Se scaffold are less cytotoxic toward mammalian cells when compared with that of CS-Ag system. 4. Conclusion and Future Prospective Similarly, Ramya et al. 204 explored in-vivo impact of biosynthesized Se nanoparticles stabilized with streptomyces Selenium is an essential micronutrient required for proper minutiscleroticus M10A62 (spherical size) on Swiss albino mice functioning of biological and metabolic mechanism within for wound treatment. The obtained result demonstrated that human body. Deficiency of selenium leads to the generation of high dose of SeNPs (10 %) ointment effectively and quickly several harmful disorders such as cancer, neurological, healed the wound. muscular, and immune disorders etc. Generally, selenium can Selenium has been additionally found to have a be depicted within very narrow concentration range due to its chemoprotective job against chemotherapy-prompted toxicity. deficiency, physiological effect, and toxic doses. At optimal Bhattacharjee et al. 205 examined Swiss albino mice for treating doses Se acts as an antioxidant, whereas at higher doses it cyclophosphamide (CP)- prompted hepatotoxicity and shows pro-oxidant activity. To overcome this issue, a precisely genotoxicity by utilizing SeNPs. In the mice, SeNPs switched or controlled dosage of Se is generally suggested. Selenium has potentially enhanced the impacts of CP-instigated toxicity: various health advantages because of its bioavailability in the rebuilding of cell reinforcement protein activity, decrease in form of selenoproteins as well as lower molecular weight. reactive oxygen species, glutathione levels, and chromosomal Various selenoproteins (Se1P, Se1F, Se1S, Se1M), thioredoxin variation in bone marrow, and DNA damage 205. Further, in reductases, glutathione peroxidases show redox activity and another study they found that SeNPs also possesses control redox reactions in cell. However, concern related to chemosensitizing and chemoprotective activity. After injecting selenium toxicity lead researchers to focus on nano-selenium. SeNPs adjuvant treatment with cyclophosphamide into ehrlich's The present review emphasized on the various method used for ascites carcinoma (EAC) containing Swiss albino mice, following the synthesis of selenium nanoparticles specially focused on changes were observed: a critical decrease in practical tumor biogenic methods and their biological applications. Biogenic cell count, packed cell and tumor volume, while an increment in methods have more advantages over chemical reduction tumor-bearing hosts survivability 206. Gao et al. 207 reported methods due to their higher biocompatibility, bioactivity, lower SeNPs as an effective chemotherapy protective agent against cytotoxicity. Biological synthesis is economical, eco-friendly and chemotherapy-prompted toxicity of irinotecan by both in-vivo safe unlike chemical reduction techniques requiring hazardous and in-vitro studies. chemicals, high temperatures and acidic pH. Use of plant In another study, it was found that red-allotrope of selenium extracts, however, is more favourable in comparison to the nanoparticles (rSeNPs) show higher cytotoxicity towards head bacterial path as it eliminates the tedious procedures and cost and neck squamous cell carcinoma (HNSCC) than human dermal for maintaining the cell cultures. fibroblast (HDF) cells, which resulted in cell proliferation 208. SeNPs has various biological applications due to its excellent Additionally, SeNPs can be used as a potential candidate in properties. SeNPs plays a key role in various biological applications due to its association with various moieties such as 12 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 20xx Please do not adjust margins
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