Side-Chain Selenium-Grafted Polymers Combining Antiangiogenesis Treatment with Photodynamic Therapy and Chemotherapy.

The abnormal tumor vasculature in solid tumors creates hypoxia and leads to compromising the delivery and anticancer efficiency of nanomedicine. Nanomaterials with intrinsic antiangiogenesis ability might normalize tumor vessels and improve the therapeutic effect of O2-related treatment like PDT. Herein, we designed and prepared ROS-responsive side-chain selenium-grafted polymers, which had potential antiangiogenic activity, as vehicles to load photodynamic therapeutic agent Ce6 and chemotherapeutic drug oridonin. Under NIR irradiation, the C-Se bonds on the side chain of polymers could be cleaved in the presence of 1O2 produced by Ce6 and further formed organic selenic acid through selenoxide elimination reaction. The generated seleninic acid could downregulate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to inhibit angiogenesis and further relieve hypoxia. The released oridonin could significantly increase the intracellular ROS concentration. Both could modulate cancer cells' microenvironment to reinforce PDT. Therefore, these nanomedicines could be a good candidate for synergistic treatments of antiangiogenesis treatment, PDT, and chemotherapy.

Selenium-doped hydroxyapatite nanoparticles for potential application in bone tumor therapy.

In the present study we have studied the incorporation and release of selenite ions (SeO32-) in hydroxyapatite nanoparticles for the treatment of bone tumors. Two types of selenium-doped hydroxyapatite (HASe) nanoparticles (NPs) with a nominal Se/(P + Se) molar ratio ranging from 0.01 up to 0.40 have been synthesized by a new and mild wet method. The two series of samples were thoroughly characterized and resulted to be slightly different in chemical composition, but they had similar properties in terms of morphology and degree of crystallinity. Selenium release from HASe was investigated under neutral and acidic conditions to simulate both healthy tissues and the low-pH environment surrounding a tumor mass, respectively. The comparison of the release profiles at two pH values clearly showed the possibility of modulating the Se release by simply changing the amount of Se in the HASe particles. The correlation between the physicochemical properties of HASe and their dissolution as a function of pH has been also investigated to facilitate future application of the NPs as chemotherapeutic adjuvant agents. Finally, the cytotoxic activity of HASe was evaluated using prostate (PC3) and breast (MDA-MB-231) cancer cells as well as healthy human bone marrow stem cells (hBMSc). HASe NPs exerted a good cytocompatibility at low concentration of Se but, with high Se doping concentration, they displayed strong cytotoxicity.

Sustainable approach to almond skin mediated synthesis of tunable selenium microstructures for coating cotton fabric to impart specific antibacterial activity.

Currently, the synthesis of nanostructured inorganic materials with tunable morphology is still a great challenge. In this study, almond skin extract was employed for the biogenic synthesis of selenium nanoparticles with tunable morphologies such as rods and brooms. The effects of various synthesis parameters on morphologies were investigated using UV-Visible spectroscopy and scanning electron microscopy (SEM) which indicated that selenium brooms (SeBrs) were best synthesized using almond skin extract and optimized conditions of SeO2, ascorbic acid, pH, incubation temperature and time. Based on these results, the mechanism of SeBrs synthesis is proposed as having involved four stages such as nucleation, self-assembly, Ostwald ripening, and decomposition. Further, the test of antibacterial activity together with minimum inhibitory concentrations and minimum bactericidal concentrations indicated the selective, specific and good activity against B. subtilis. In addition, in situ coating of SeBrs on cotton fabric and its investigation by SEM demonstrated successful coating. Evident from plate-based assay and study of growth kinetics, coated fabric exhibited excellent anti-B. subtilis activity which demonstrated that biogenic SeBrs can be employed to coat cotton fabrics that can be used in operation theatres to reduce the episodes of Bacillus related Bacteraemia.

Protective role of biogenic selenium nanoparticles in immunological and oxidative stress generated by enrofloxacin in broiler chicken.

Presently most bacteria are becoming antibiotic resistant. Due to this there is a deficiency of potent antibiotics, therefore we have to preserve and improve the efficiency of existing antibiotics by mitigating the side effects. Enrofloxacin (EFX) is an important antimicrobial used in veterinary practice but it is known to exert immune suppression antioxidant stress. In the present study, we report on: (a) the biosynthesis of selenium nanoparticles (Se NPs), and (b) their protective effect in reducing adverse effects of EFX on broiler chicken. A potent bacterial strain, isolated from farm soil, has been identified as Pantoea agglomerans (GenBank: KU500622). It tolerates a high concentration of selenium dioxide (9 mM) and produces Se NPs under aerobic conditions. The obtained Se NPs are amorphous in structure and spherical in shape with sizes of less than 100 nm. The activity of cellular, humoral immune response and enzymatic and non-enzymatic antioxidants, has significantly been decreased as a result of EFX treatment. We investigated that Se NP supplementation greatly restores these values towards the control, and to even higher than those of the control. Adverse effects of EFX are prevented by simultaneous exposure to Se NPs (0.6 mg per kg of feed) in the diet of poultry chicken.

Divergent Reactivity of Amino Acid Alkyl Ester Hydrochlorides with 2-Oxoaldehydes: Role of Selenium Dioxide To Promote Regioselective Synthesis of Imidazoles.

Novel amino acid substituted imidazoles engendered from amino acid alkyl ester hydrochlorides and 2-oxoaldehydes as a result of selenium dioxide promoted unconventional reaction in a basic environment is presented for the first time. Despite the nature of the 2-oxoaldehydes/amino acids used, the imidazoles generated had a functional core structure, and all of the reactions meticulously retained regioselectivity. The imperative feature of these reactions was the uniqueness of selenium dioxide in fixing two nitrogen atoms from amino acids through an in situ generated ArCOCHN1N2 system.

Effects of selenizing angelica polysaccharide and selenizing garlic polysaccharide on immune function of murine peritoneal macrophage.

The effects of two selenizing polysaccharides (sCAP2 and sGPS6) on immune function of murine peritoneal macrophages taking two non-selenizing polysaccharides (CAP and GPS) and modifier Na2SeO3 as control. In vitro test, the changes of selenizing polysaccharides, non-selenizing polysaccharides and Na2SeO3 on murine macrophages function were evaluated by phagocytosis and nitric oxide (NO) secretion tests. In vivo test, the mice were injected respectively with 0.2, 0.4 and 0.6 mg of sCAP2, sGPS6, CAP and GPS, or Na2SeO3 80 µg or normal saline 0.4 mL. The peritoneal macrophages were collected and cultured to determine the contents of TNF-α, IL-6 and IL-10 in supernatants by enzyme-linked immunosorbent assay. The results showed that sCAP2 and sGPS6 could significantly promote the phagocytosis and secretion of NO and three cytokines of macrophages in comparison with CAP and GPS. sCAP2 possessed the strongest activity. This indicates that selenylation modification can further improve the immune-enhancing activity of polysaccharide, and sCAP2 could be as a new immunopotentiator.

Simple synthesis of luminescent CdSe quantum dots from ascorbic acid and selenium dioxide.

A simple, low-cost and convenient method was developed for the synthesis of highly luminescent CdSe quantum dots (QDs) in an aqueous medium. Compared with previous methods, this synthesis was carried out in one pot using ascorbic acid (C6H8O6) to replace NaBH4 or N2H4·H2O as a reductant, and selenium dioxide to replace selenium or its other hazardous, expensive and unstable compounds as a precursor. The mechanism of CdSe QDs formation was elucidated. The influence of various experimental variables, including refluxing time, Cd/MSA and Cd/Se molar ratios, on the luminescent properties of the QDs were systematically investigated. X-Ray powder diffraction and transmission electron microscopy characterization indicated that the QDs had a pure cubic zinc-blended structure with a spherical shape.

Anti-biofilm activity of biogenic selenium nanoparticles and selenium dioxide against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis.

The aim of the present study was to investigate the anti-biofilm activity of biologically synthesized selenium nanoparticles (Se NPs) against the biofilm produced by clinically isolated bacterial strains compared to that of selenium dioxide. Thirty strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis were isolated from various specimens of the patients hospitalized in different hospitals (Kerman, Iran). Quantification of the biofilm using microtiter plate assay method introduced 30% of S. aureus, 13% of P. aeruginosa and 17% of P. mirabilis isolates as severely adherent strains. Transmission electron micrograph (TEM) of the purified Se NPs (produced by Bacillus sp. MSh-1) showed individual and spherical nano-structure in the size range of 80-220nm. Obtained results of the biofilm formation revealed that selenium nanoparticles inhibited the biofilm of S. aureus, P. aeruginosa, and P. mirabilis by 42%, 34.3%, and 53.4%, respectively, compared to that of the non-treated samples. Effect of temperature and pH on the biofilm formation in the presence of Se NPs and SeO2 was also evaluated.

The influence of selenium addition during germination of Brassica seeds on health-promoting potential of sprouts.

The correlation among selenium uptake, the content of bioactive compounds in sprouts, and biological activities triggered in cultured human cells by sprout extracts was investigated. Seeds of Brassica crops and rye were treated with SeO2 water solution. The selenium levels in sprouts increased from 1.0-4.1 to 53.3-382 µg/g dw with no influence on plant physiology according to the indices used. Neither the composition of glucosinolates (GL) in Brassica sprouts nor the myrosinase activity nor the composition of GL breakdown lipophilic products were significantly affected. In all Brassica sprouts, conversion to health-promoting isothiocyanates (ITC) and indoles corresponded to only 1% of total GLs. Low ITC concentration may explain observed lack of induction of glutathione S-transferases (GST) and quinone oxidoreductase (NQO) detoxifying enzymes in HT29 cells exposed to sprout extracts. The insignificant impact on cell growth and genome function suggests that Brassica sprouts may be safe vehicle of selenium to combat its dietary deficiency.

A reversible fluorescent probe for detecting hypochloric acid in living cells and animals: utilizing a novel strategy for effectively modulating the fluorescence of selenide and selenoxide.

Based on a novel strategy for modulating the fluorescence of selenide and selenoxide, we have designed and developed a reversible fluorescent probe for hypochloric acid. And the synthesis, characterization, fluorescence properties, as well as the biological applications in living cells and animals, have all been described.

Acute and subacute toxicity of novel biogenic selenium nanoparticles in mice.

CONTEXT: In the present investigation, acute and subacute toxicity of the biogenic Se nanoparticles (Se NPs) has been reported. OBJECTIVE: To characterize the Se NPs produced by a bacterium species and to evaluate their toxicity and impact on clinical chemistry and hematological parameters of NMRI mice. MATERIALS AND METHODS: The Se NPs were prepared by Bacillus sp. MSh-1 in a culture medium containing SeO(2) (1.26 mM) and their physiochemical properties investigated using TEM, XRD and FT-IR. The LD(50) of Se NPs and SeO(2) were determined and the subacute toxicity evaluated by orally administration of 0, 2.5, 5, 10 and 20 mg kg(-1) of Se NPs to male mice for 14 consecutive days. Parameters of blood cells, AST, ALT, ALP, creatinine, BUN, cholesterol, bilirubin, triglyceride and CPK were experimentally measured. RESULTS: The XRD and TEM analyses showed that the spherical NPs were amorphous, in the size range of 80-220 nm. The toxicological evaluation showed that the LD(50) values of SeO(2) and Se NPs were 7.3 and 198.1 mg kg(-1), respectively. No biochemical changes were observed from the administration of 2.5, 5 and 10 mg kg(-1) of Se NPs, but a dose of 20 mg kg(-1) was accompanied with signs of toxicity including lower body weight and changes in clinical chemistry and hematological parameters. CONCLUSION: The biogenic Se NPs were less toxic than synthetic Se NPs and much less (26-fold) toxic than the SeO(2), which demonstrates the important role of Bacillus sp. MSh-1 in conversion of a highly toxic Se compound to the less toxic Se NPs.

Selenium accumulation, distribution, and speciation in spineless prickly pear cactus: a drought- and salt-tolerant, selenium-enriched nutraceutical fruit crop for biofortified foods.

The organ-specific accumulation, spatial distribution, and chemical speciation of selenium (Se) were previously unknown for any species of cactus. We investigated Se in Opuntia ficus-indica using inductively coupled plasma mass spectrometry, microfocused x-ray fluorescence elemental and chemical mapping (µXRF), Se K-edge x-ray absorption near-edge structure (XANES) spectroscopy, and liquid chromatography-mass spectrometry (LC-MS). µXRF showed Se concentrated inside small conic, vestigial leaves (cladode tips), the cladode vasculature, and the seed embryos. Se K-edge XANES demonstrated that approximately 96% of total Se in cladode, fruit juice, fruit pulp, and seed is carbon-Se-carbon (C-Se-C). Micro and bulk XANES analysis showed that cladode tips contained both selenate and C-Se-C forms. Inductively coupled plasma mass spectrometry quantification of Se in high-performance liquid chromatography fractions followed by LC-MS structural identification showed selenocystathionine-to-selenomethionine (SeMet) ratios of 75:25, 71:29, and 32:68, respectively in cladode, fruit, and seed. Enzymatic digestions and subsequent analysis confirmed that Se was mainly present in a "free" nonproteinaceous form inside cladode and fruit, while in the seed, Se was incorporated into proteins associated with lipids. µXRF chemical mapping illuminated the specific location of Se reduction and assimilation from selenate accumulated in the cladode tips into the two LC-MS-identified C-Se-C forms before they were transported into the cladode mesophyll. We conclude that Opuntia is a secondary Se-accumulating plant whose fruit and cladode contain mostly free selenocystathionine and SeMet, while seeds contain mainly SeMet in protein. When eaten, the organic Se forms in Opuntia fruit, cladode, and seed may improve health, increase Se mineral nutrition, and help prevent multiple human cancers.

Differential patterns of accumulation and depuration of dietary selenium and vanadium during metamorphosis in the Gray Treefrog (Hyla versicolor).

Selenium (Se) and vanadium (V) are contaminants commonly found in aquatic systems affected by wastes derived from fossil fuels. To examine their effects on a widely distributed species of amphibian, we exposed gray tree frogs (Hyla versicolor) to Se (as SeO2) or V (as NaVO3) in their diet from the early larval period to metamorphosis. Concentrations of Se in Se-enriched food were 1.0 (Se control), 7.5 (Se low), and 32.7 (Se high) µg/g dw. Concentrations of V in V-enriched food were 3.0 (V control), 132.1 (V low), and 485.7 (V high) µg/g dw. Although we observed bioaccumulation of both metals throughout the larval period, no effects on growth, survival, metabolic rate, or lipid content were observed. Se concentrations in tissues did not vary among life stages, neither in Se low nor Se high treatments, such that maximum accumulation had occurred by the mid-larval period. In addition, there was no evidence of depuration of Se in either the Se low or the Se high treatments during metamorphosis. A strikingly different pattern of accumulation and depuration occurred in V-exposed individuals. In treatments V low and V high, maximum body burdens occurred in "premetamorphs" (i.e., animals with developed forelimbs but in which tail resorption had not begun), whereas body burdens in animals having completed metamorphosis were much lower and similar to those in larvae. These results suggest that compared with Se-exposed animals, V-exposed animals were able to depurate a substantial amount of accumulated V during the metamorphic period. In an ecologic context, it appears that amphibians exposed to Se during the larval period may serve as a vector of the metal to terrestrial predators, yet potential transfer of accumulated V to predators would largely be restricted to the aquatic habitat.

Abiotic formation of elemental selenium and role of iron oxide surfaces.

The possible abiotic reduction of selenite to form elemental Se was studied under controlled conditions in the presence of ferrous iron. The reduction of selenite and formation of Se (0) was found to be a surface-mediated reaction by iron oxides. Without the presence of the reactive surface of freshly precipitated iron oxides, the reduction reaction could not be detected, even under a well controlled low oxygen environment (30 ppmv). Our results clearly illustrate the crucial role of iron oxide in this redox process. In lake sediments, the complex sediment matrix seems to strongly adsorb SeO(2-) and make it less available for reduction into Se(0). When lake sediments were submitted to UV irradiation to eliminate bacteria, the percentage of iron oxides increased and it was found that higher levels of iron oxides, generated by the UV treatment, correlated with the higher formation of Se(0). Moreover, the results of our field studies on two distinctively different lake sediments also showed a strong influence of iron oxides on the formation of elemental Se, which agrees well with our laboratory simulations.

Cellulose acetate-directed growth of bamboo-raft-like single-crystalline selenium superstructures: high-yield synthesis, characterization, and formation mechanism.

High-yield synthesis of bamboo-raft-like single-crystalline selenium superstructures has been realized for the first time via a facile solvothermal approach by reducing SeO2 with ethylene alcohol in the presence of cellulose acetate. The formation of a raftlike superstructure with various forms is strongly dependent on the temperature, amount of cellulose acetate, reaction time, and even preheating treatment. The suitable amount of cellulose acetate is essential for the formation of elegant and uniform raft Se. The morphology, microstructure, optical properties, and chemical compositions of bamboo-raft-like selenium were characterized using various techniques (X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy (TEM), high-resolution (HR) TEM, X-ray photoelectron spectroscopy, UV-vis spectroscopy, FTIR spectroscopy, and Raman spectroscopy). A possible growth mechanism has been proposed. Such special superstructures could provide a useful precursor for potential applications.

Identification of selenium species in selenium-enriched Lens esculenta plants by using two-dimensional liquid chromatography-inductively coupled plasma mass spectrometry and [77Se]selenomethionine selenium oxide spikes.

Selenium speciation in Se-enriched Lens esculenta grown in hydroponic culture containing inorganic selenium as Na(2)SeO(3) and Na(2)SeO(4) was performed. After 16 days of growth, the plants were collected and divided in two parts, roots and stems and then analysed to identify and quantify selenium species. Speciation studies of the enzymatic extracts were carried out by using anion-exchange (PRP-X100) and size-exclusion/ion-exchange (Shodex Asahipak) columns coupled to inductively coupled plasma mass spectrometry (ICP-MS). The need of using two independent chromatographic mechanisms for unambiguous species identification is demonstrated. Moreover, the use of a [(77)Se]selenomethionine selenium oxide spike turned out to be critical to discriminate between selenium selenomethioine selenium oxide and selenocysteine.

Simultaneous removal of SO2 and trace SeO2 from flue gas: effect of SO2 on selenium capture and kinetics study.

Sulfur dioxide (SO2) and trace elements are all pollutants derived from coal combustion. This study relates to the simultaneous removal of SO2 and trace selenium dioxide (SeO2) from flue gas by calcium oxide (CaO) adsorption in the moderate temperature range, especially the effect of SO2 presence on selenium capture. Experiments performed on a thermogravimetric analyzer (TGA) can reach the following conclusions. When the CaO conversion is relatively low and the reaction rate is controlled by chemical kinetics, the SO2 presence does not affect the selenium capture. When the CaO conversion is very high and the reaction rate is controlled by product layer diffusion, the SO2 presence and the product layer diffusion resistance jointly reduce the selenium capture. On the basis of the kinetics study, a method to estimate the trace selenium removal efficiency using kinetic parameters and the sulfur removal efficiency is developed.

Acute oral selenium intoxication with ten times the lethal dose resulting in deep gastric ulcer.

A 48-year-old woman presented after taking 2000 mg of selenium dioxide, corresponding to 10 times the experimental lethal dose in animals. She presented with mildly altered consciousness and hematemesis. Endoscopy revealed mucosal damage throughout the oral cavity, esophagus, and stomach. There was no evidence of perforation. After intubation and gastric lavage, hemodialysis was performed. The patient was discharged uneventfully on the 16(th) day. This case highlights a very rare acute selenium intoxication. Serum and urinary selenium levels and serum glutathione peroxidase activities during the patient's course were followed, as well as the mucosal corrosive damage caused by the selenium.

A simple synthesis of 7,4'-dihydroxy-6-methoxyisoflavone, glycitein, the third soybean isoflavone.

4-Methoxyresorcinol (3) was synthesized as the precursor for glycitein (6) synthesis by the oxidation of 3-hydroxy-4-methoxybenzaldehyde (1) to the aryl formate with H2O2 and a catalytic amount of SeO2. Glycitein (6) was synthesized by cyclization of 2,4,4'-trihydroxy-5-methoxydeoxybenzoin (5) with N,N-dimethylformamide, boron trifluoride diethyl ether, and methanesulfonyl chloride in a microwave oven.

Protective effects of selenium against mercury toxicity in cultured Atlantic spotted dolphin (Stenella plagiodon) renal cells.

Marine mammals are known for their low susceptibility to mercury toxicity, and selenium may play a role in this protection against mercury intoxication. To gain insight into mechanisms by which selenium might inhibit mercury toxicity in cetacean cells, we investigated the effects of sodium selenite on cell proliferation and cell death (including apoptosis, oncosis, and necrosis) of control and mercuric chloride-treated Atlantic spotted dolphin renal cells (Sp1K cells). Concurrent exposure to 80 microM Na2SeO3 provided full protection against the decrease in cell proliferation induced by 20 microM HgCl2. Pretreatment with Na2SeO3 increased the protective effects of selenium administered later in conjunction with mercury, but pretreatment alone did not provide protection against mercury given alone. Furthermore, Na2SeO3 administered after the exposure to HgCl2 did not protect cells. These data suggest that the coexistence of Na2SeO3 and HgCl2 was essential for the protective effects of Na2SeO3 against the toxicity of HgCl2 in Sp1K cells, and may involve selenium-mercury binding. This is supported by the results of an experiment in which earlier premixed mercury and selenium solutions were less cytotoxic than freshly mixed solutions. Furthermore, HgCl2 induced apoptosis in Sp1K cells, as revealed by nuclear specific dye (7-AAD) incorporation and cell flow cytometry, and this was prevented by the concurrent exposure to Na2SeO3. Inhibition of mercury-induced apoptosis in marine mammal cells, provided by selenium, may contribute to the in vivo protection. This study is the first report that addresses the mechanism of mercury-selenium antagonism in cultured cetacean cells at the cellular level.