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Enrichment of selenium (Se) by seaweed is of great significance for mariculture. In this study, the green alga Ulva fasciata was cultured with a selenite (NaSeO) concentration from 0 to 1,250 mg L. Se accumulation in the algal biomass was linearly related to NaSeO concentration in the culture medium. Lower Se concentrations (≤750 mg L) increased the activities of guaiacol peroxidase (GPX), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) and the content of photosynthetic pigments, and as well induced lipid peroxidation (LPO) and intracellular reactive oxygen species (ROS) levels. Meanwhile, the cell growth rate and concentrations of organic Se increased. In contrast, these changes were the opposite in U. fasciata exposed to Se concentrations higher than 750 mg L. In all cases, Se- Ulva was able to remove inorganic nutrients effectively. Therefore, U. fasciata is tolerant to Se, and Se- Ulva has potential as a source of antioxidative food and an effective control of eutrophication. [ABSTRACT FROM AUTHOR]

Abstract: A simple and solution-phase approach for large-scale synthesis of selenium nanoparticles (Nano-Se) by reducing sodium selenite (Na2SeO3) with l-cysteine has been demonstrated in this study. l-cysteine was used as both the reducing agent and surface modifier to control the formation of Nano-Se. The effects of reactant concentrations and ratios, and reaction time on the size and stability of Nano-Se were also investigated. The morphology and chemical composition of Nano-Se were characterized using various spectroscopic and microscopic methods. The results showed that varying the concentration ratio of l-cysteine to Na2SeO3 could control the diameter and morphology of Nano-Se, but not affecting their crystalline phases and chemical compositions. Monodisperse and homogeneous spherical Nano-Se with an average diameter of about 100nm could be synthesized with the concentration ratio of l-cysteine to Na2SeO3 at 4:1. A striking feature of the as-synthesized Nano-Se was their good stability when dispersed in the reaction solutions, which indicates their potential in medical applications. [Copyright &y& Elsevier]

Abstract: Selenadiazole derivative is one kind of synthetic organoselenium compounds with potent and broad-spectrum antitumor activity. In this study, we showed that anthrax [1,2-c] [1,2,5] selenadiazolo-6,11-dione (ASDO), an novel selenadiazole derivative, induced time- and dose-dependent apoptotic cell death in MCF-7 human breast carcinoma cells, as indicated by accumulation of sub-G1 cell population, DNA fragmentation, nuclear condensation, caspase activation and PARP cleavage. ASDO-induced apoptosis was significantly inhibited by a general caspase inhibitor z-VAD-fmk, demonstrating the important role of caspases in ASDO-induced apoptotic pathway. Treatment of MCF-7 cells with ASDO resulted in a rapid depletion of mitochondrial membrane potential and release of cytochrome c and Smac/Diablo through up-regulation of Bax, Bad and PUMA expression and down-regulation of Bcl-xl expression. Moreover, ASDO treatment up-regulated the expression levels of total p53 and its target gene p21Waf1. Silencing of p53 activation with RNA interference effectively blocked the ASDO-induced cell PARP cleavage, DNA fragmentation and caspase activation. Furthermore, ASDO-induced apoptosis was interestingly found to be independent of reactive oxygen species production. Taken together, we conclude that ASDO induces MCF-7 cell apoptosis through a p53-dependent and mitochondria-mediated pathway. [Copyright &y& Elsevier]

Abstract: Epidemiological and clinical studies have demonstrated that dietary supplementation of selenium (Se) could reduce the incidence of human cancers. In this study, selenocystine, a nutritionally available selenoamino acid, was identified as a novel agent with broad-spectrum antitumor activity. A panel of eight human caner cell lines was shown to be susceptible to selenocystine, with IC50 values ranging from 3.6 to 37.0μM. Selenocystine induced dose-dependent apoptosis in A375, HepG2 and MCF7 cells was evaluated by flow cytometric analysis and annexin-V staining assay. Mechanistic studies showed time- and dose-dependent increases in intracellular reactive oxygen species (ROS) in susceptible cancer cells (MCF7 and HepG2 cells) treated with selenocystine. However, selenocystine-induced ROS overproduction was not observed in non-susceptible normal human fibroblast Hs68 cells. Significant DNA strand breaks were observed in selenocystine-treated MCF7 and HepG2 cells as examined by single-cell gel electrophoresis (Comet assay). The thiol-reducing antioxidants, glutathione and N-acetylcysteine, inhibited intracellular ROS generation, DNA strand breaks and accumulation of sub-G1 population in MCF7 cells exposed to selenocystine. Our results suggest a possible role of ROS as a mediator of the signaling pathway of selenocystine-induced, DNA damage–mediated apoptosis in susceptible cancer cells. [Copyright &y& Elsevier]

Abstract: Selenium nanoparticle (Nano-Se) is a novel Se species with novel biological activities and low toxicity. In the present study, we demonstrated a simple method for synthesis of size-controlled Nano-Se by adding Undaria pinnatifida polysaccharides to the redox system of selenite and ascorbic acid. A panel of four human cancer cell lines was shown to be susceptible to Nano-Se, with IC50 values ranging from 3.0 to 14.1μM. Treatment of A375 human melanoma cells with the Nano-Se resulted in dose-dependent cell apoptosis as indicated by DNA fragmentation and phosphatidylserine translocation. Further investigation on intracellular mechanisms found that Nano-Se treatment triggered apoptotic cell death in A375 cells with the involvement of oxidative stress and mitochondrial dysfunction. Our results suggest that Nano-Se may be a candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancers, especially melanoma cancer. [Copyright &y& Elsevier]

Abstract: The role of organoselenium compounds as potent cancer chemopreventive and chemotherapeutic agents has been supported by epidemiological, preclinical and clinical studies. In this study, a novel selenadiazole derivative, 1,2,5-selenadiazolo-[3,4-d]pyrimidine-5,7-(4H,6H)-dione (SPO), is identified as a potent antiproliferative agent against human breast adrenocarcinoma MCF-7 cells, human hepatoma HepG2 cells and human melanoma A375 cells. Induction of apoptosis in MCF-7 and A375 cells by SPO was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Further investigation on intracellular mechanisms found that SPO treatments induced activation of caspase-8 and caspase-9, overproduction of reactive oxygen species, and depletion of mitochondrial membrane potential (ΔΨm) through regulating the expression of pro-survival and pro-apoptotic Bcl-2 family members. Our findings suggest that SPO is a promising novel organoselenium compound with potential in the treatment of human cancers. [Copyright &y& Elsevier]

Abstract: Accumulation of Se in mixotrophic culture of Spirulina platensis was investigated in this study. Results indicated that glucose was better than acetate as an organic carbon source for mixotrophic culture of S. platensis. Supplementation of glucose (2gL−1) significantly enhanced the biomass concentration (2.57gL−1) and the production of phycocyanin (0.279gL−1) and allophycocyanin (0.126gL−1) in S. platensis, which were much higher than those of photoautotrophic culture (1.08gL−1, 0.119gL−1 and 0.042gL−1, respectively). Stepwise addition of Se during the growth phase avoided the inhibitory effect of high Se concentration on the growth of S. platensis. The Se enrichment favored the production of phycocyanin and allophycocyanin in the algal cells. The highest Se yield (1033μgL−1) was obtained at an accumulative Se concentration of 250mgL−1, with organic Se percentage, biomass concentration, phycocyanin and allophycocyanin yields of 92.3%, 2.55gL−1, 0.295gL−1 and 0.153gL−1, respectively. These results indicated that the application of mixotrophic culture S. platensis with stepwise addition of Se to the medium could offer an effective and economical way for the production of high Se-enriched algal products. [Copyright &y& Elsevier]

Abstract: A fast protein liquid chromatographic method for purification of selenium-containing phycocyanin (Se-PC) from selenium-enriched Spirulina platensis was described in this study. The purification procedures involved fractionation by ammonium sulfate precipitation, DEAE-Sepharose ion-exchange chromatography and Sephacry S-300 size exclusion chromatography. The purity ratio (A 620/A 280) and the separation factor (A 620/A 655) of the purified Se-PC were 5.12 and 7.92, respectively. The Se concentration of purified Se-PC was 496.5μg g−1 protein, as determined by ICP-AES analysis. The purity of the Se-PC was further characterized by UV–VIS and fluorescence spectrometry, SDS–PAGE, RP-HPLC and gel filtration HPLC. The apparent molecular mass of the native Se-PC determined by gel filtration HPLC was 109kDa, indicating that the protein existed as a trimer. SDS–PAGE of the purified Se-PC yielded two major bands corresponding to the α and β subunits. A better separation of these two subunits was obtained by RP-HPLC. Identification of the α and β subunits separated by SDS–PAGE and RP-HPLC was achieved by peptide mass fingerprinting (PMF) using MALDI-TOF-TOF mass spectrometry. [Copyright &y& Elsevier]

Abstract: The feasibility of mixotrophic culture of high selenium-enriched Spirulina platensis was investigated in this study. The results indicated that supplementation of acetate to the mixotrophic culture of S. platensis led to a significant enhancement in biomass concentration, chlorophyll a, lutein, β-carotene, phycocyanin and allophycocyanin production when compared to the photoautotrophic culture. Stepwise addition of selenium (Se) source during the exponential growth phase of S. platensis can avoid the inhibitory effect of high Se concentration on cell growth. At an accumulative Se concentration of 450mgL−1 under mixotrophic culture conditions, the highest Se yield was obtained; while significant enhancement in Se accumulation capability, algal biomass concentration and photosynthetic pigment yield was also observed. These results indicated that the application of mixotrophic culture with stepwise addition of Se to culture of S. platensis offers a more effective and economical way for the production of high Se-enriched biological compounds. [Copyright &y& Elsevier]

Gracilaria is the second most productive genus of mariculture seaweeds after Laminaria in China. It is important to increase its economic value. The purpose of this study was to document the accumulation and biotransformation of selenium in Gracilaria lemaneiformis. The seaweed was cultured for 12 days in medium containing from 0 to 2000 mg L−1 selenite. At concentrations lower than 750 mg L−1, seaweed growth was promoted and the amount of chlorophyll a decreased. The organic Se content in the seaweed was over 80% in all groups and was as much as 400 μg g−1 of dry weight. Se enrichment induced a decrease in the activities of superoxide dismutase in the seaweed cells. These results suggest that G. lemaneiformis is tolerant to Se and prevents phytotoxicity by altering various metabolic processes. Furthermore, this seaweed exhibits great potential to transform inorganic Se into the organic form and therefore could be a safe candidate for the production of Se-enriched functional food. [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC)‐induced osteoporosis (GIO) is a concurrent disease commonly appeared in chronic inflammatory and autoimmune disease patients. Stereoselective recognition between chiral drugs and homochiral biological molecules could directly affect their distribution, adhesion and transport. Herein, trace element selenium (Se) with bone formation‐regulating activity, is employed to construct cysteine‐decorated chiral nanoparticles (Cys@SeNPs) to attenuate GIO. Interestingly, comparing with the racemic (DL‐Cys@SeNPs) and D‐Cys@SeNPs, the L‐Cys@SeNPs displays higher uptake in osteoblast cells and could lessen reactive oxygen species overproduction to block dexamethasone (Dex)‐induced osteoblasts cells apoptosis. Intracellular L‐Cys@SeNPs could be predominantly transformed to selenocystine to upregulate the expression levels of antioxidative selenoproteins to effectively scavenge Dex‐induced excessive ROS accumulation in osteoblasts, and thus reduce the undesirable apoptosis through activating Wnt/β‐catenin pathway. Consistently, L‐Cys@SeNPs significantly alleviates the main osteoporosis symptoms of bone trabeculae destruction and decreased bone density in vivo, and also reduces the weight gain and fatty liver formation in Dex‐exposed mice, thus suppressing the overall side effects of Dex. This study not only demonstrates an effective strategy for treatment of GIO by using chiral Se nanomedicine, but also elucidates the important roles of selenoproteins in alleviating osteoporosis, which could help for future Se‐based drug design through chirality control engineering. [ABSTRACT FROM AUTHOR]

The incidence and mortality rates of lung cancer are among the highest in the world. Traditional treatment methods include surgery, chemotherapy, and radiotherapy. Although rapid progress has been achieved in the past decade, treatment limitations remain. It is therefore imperative to identify safer and more effective therapeutic methods, and research is currently being conducted to identify more efficient and less harmful drugs. In recent years, the discovery of antitumor drugs based on the essential trace element selenium (Se) has provided good prospects for lung cancer treatments. In particular, compared to inorganic Se (Inorg-Se) and organic Se (Org-Se), Se nanomedicine (Se nanoparticles; SeNPs) shows much higher bioavailability and antioxidant activity and lower toxicity. SeNPs can also be used as a drug delivery carrier to better regulate protein and DNA biosynthesis and protein kinase C activity, thus playing a role in inhibiting cancer cell proliferation. SeNPs can also effectively activate antigen-presenting cells to stimulate cell immunity, exert regulatory effects on innate and regulatory immunity, and enhance lung cancer immunotherapy. This review summarizes the application of Se-based species and materials in lung cancer diagnosis, including fluorescence, MR, CT, photoacoustic imaging and other diagnostic methods, as well as treatments, including direct killing, radiosensitization, chemotherapeutic sensitization, photothermodynamics, and enhanced immunotherapy. In addition, the application prospects and challenges of Se-based drugs in lung cancer are examined, as well as their forecasted future clinical applications and sustainable development. [ABSTRACT FROM AUTHOR]

Selenium nanoparticle (SeNP)-based nanotherapeutics have become an emerging cancer therapy, while effective drug delivery remains a technical hurdle. A theranostic approach, through which imaging companions are integrated with SeNPs, will allow image-guided drug delivery and, therefore, is highly desirable. Traditional methods require the chemical conjugation of imaging agents to the surface of nanoparticles, which may impede the later clinical translation. In this study, we developed a label-free strategy in which lentinan-functionalized SeNPs (LNT-SeNPs) are detected using MRI by the hydroxyl protons carried on LNT molecules. The in vitro phantom study showed that LNT and LNT-SeNPs have a strong CEST signal at 1.0 ppm apart from the water resonance, suggesting an in vivo detectability in the µM concentration range. Demonstrated on CT26 colon tumor cells, LNT-SeNPs exert a strong anticancer effect (IC50 = 4.8 μM), prominently attributed to the ability to generate intracellular reactive oxygen species. However, when testing in a mouse model of CT26 tumors, administration of LNT-SeNPs alone was found unable to deliver sufficient drugs to the tumor, leading to poor treatment responses. To improve the drug delivery, we co-injected LNT-SeNPs and TNF-α, a previously reported drug that could effectively damage the endothelial cells in the tumor vasculature, thereby increasing drug delivery to the tumor. Our results revealed a 75% increase in the intratumoral CEST MRI signal, indicating a markedly increased delivery efficiency of LNT-SeNPs when combined with TNF-α. The combination therapy also resulted in a significantly enhanced treatment outcome, as revealed by the tumor growth study. Taken together, our study demonstrates the first label-free, SeNP-based theranostic system, in which LNT was used for both functional surface coating and CEST MRI signal generating. Such a theranostic LNT-SeNP system is advantageous because it requires chemical labeling and, therefore, has high biocompatibility and low translatable barriers. [ABSTRACT FROM AUTHOR]

Radiotherapy is still the recommended treatment for cervical cancer. However, radioresistance and radiation-induced side effects remain one of the biggest clinical problems. Selenium (Se) has been confirmed to exhibit radiation-enhancing effects for cancer treatment. However, Se species dominate the biological activities and which form of Se possesses better radiosensitizing properties and radiation safety remains elusive. Here, different Se species (the valence state of Se ranged from - 2, 0, +4 to + 6) synergy screen was carried out to identify the potential radiosensitizing effects and radiation safety of Se against cervical cancer. We found that the therapeutic effects varied with the changes in the Se valence state. Sodium selenite (+4) displayed strong cancer-killing effects but also possessed severe cytotoxicity. Sodium selenate (+6) neither enhanced the killing effects of X-ray nor possessed anticancer activity by its alone treatment. Although nano-selenium (0), especially Let-SeNPs, has better radiosensitizing activity, the - 2 organic Se, such as selenadiazole derivative SeD (-2) exhibited more potent anticancer effects and possessed a higher safe index. Overall, the selected Se drugs were able to synergize with X-ray to inhibit cell growth, clone formation, and cell migration by triggering G2/M phase arrest and apoptosis, and SeD (-2) was found to exhibit more potent enhancing capacity. Further mechanism studies showed that SeD mediated p53 pathway activation by inducing DNA damage through promoting ROS production. Additionally, SeD combined with X-ray therapy can induce an anti-tumor immune response in vivo. More importantly, SeD combined with X-ray significantly inhibited the liver metastasis of tumor cells and alleviated the side effects caused by radiation therapy in tumor-bearing mice. Taken together, this study demonstrates the radiosensitization and radiation safety effects of different Se species, which may shed light on the application of such Se-containing drugs serving as side effects-reducing agents for cervical cancer radiation treatment. [ABSTRACT FROM AUTHOR]

Abstract: A simple and rapid method has been developed to synthesize cuprous selenide (Cu2Se) nanoparticles by the reaction of selenium nanoparticles sol with copper sulfate solution containing ascorbic acid at room temperature. Cu2Se nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and energy dispersive X-ray analysis (EDX). The results indicated that Cu2Se nanoparticles were cubic crystal structure and spherical with the diameter about 75nm. The ultraviolet–visible absorption spectrum (UV–vis) and cyclic voltammetry of Cu2Se nanoparticles were also investigated. The optical band gap energy of Cu2Se nanoparticles was 1.94eV. On the basis of a series of experiments and characterizations, the formation mechanism of Cu2Se nanoparticles was discussed. [Copyright &y& Elsevier]

The chirality of nanoparticles directly influences their transport and biological effects under physiological conditions, but the details of this phenomenon have rarely been explored. Herein, chiral GSH‐anchored selenium nanoparticles (G@SeNPs) are fabricated to investigate the effect of their chirality on their transport and antioxidant activity. G@SeNPs modified with different enantiomers show opposite handedness with a tunable circular dichroism signal. Noninvasive positron emission tomography imaging clearly reveals that 64Cu‐labeled l‐G@SeNPs experience distinctly different transport among the major organs from that of their d‐and dl‐counterparts, demonstrating that the chirality of the G@SeNPs influences the biodistribution and kinetics. Taking advantage of the strong homologous cell adhesion and uptake, l‐G@SeNPs have been shown here to effectively prevent oxidation damage caused by palmitic acid in insulinoma cells. [ABSTRACT FROM AUTHOR]

The chirality of nanoparticles directly influences their transport and biological effects under physiological conditions, but the details of this phenomenon have rarely been explored. Herein, chiral GSH‐anchored selenium nanoparticles (G@SeNPs) are fabricated to investigate the effect of their chirality on their transport and antioxidant activity. G@SeNPs modified with different enantiomers show opposite handedness with a tunable circular dichroism signal. Noninvasive positron emission tomography imaging clearly reveals that 64Cu‐labeled l‐G@SeNPs experience distinctly different transport among the major organs from that of their d‐and dl‐counterparts, demonstrating that the chirality of the G@SeNPs influences the biodistribution and kinetics. Taking advantage of the strong homologous cell adhesion and uptake, l‐G@SeNPs have been shown here to effectively prevent oxidation damage caused by palmitic acid in insulinoma cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • Biological functions and chemical characteristics of Se. • Intuitionistic connections between chemical and physiological properties of Se and their biomedical applications. • Summary of research status and characteristics of fluorescent probes for active Se species. • Current challenges of fluorescent probes in specifically identifying active Se species and their biomedical application. Selenium (Se) is of fundamental importance to human health as an essential trace element, mainly through regulation of selenoproteins (SePs). Therefore, monitoring Se transformation in living systems and revealing cellular functions of SePs are of great significance for diverse disease treatment. However, the lack of probing tools for in situ monitoring of Se species severely hinders its development in bio-analysis. Thus, the discovery of fluorescent probes with specific recognition and responses to SePs/Se-containing species are promising for investigating the biological actions of Se. Herein, we summarized the chemical properties of various active Se species and discussed the rational design of basic structures of fluorescent probes for Se species and their biomedical applications. We also highlighted the key findings on fluorescent probes for Se species inside living systems, and proposed a network for rational design and biomedical applications of fluorescent probes for biological Se-containing substances. [ABSTRACT FROM AUTHOR]

Abstract: A combination of chemo‐ and photothermal therapy has emerged as a promising tactic for cancer therapy. However, the intricacy of accurate delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Hence, to assure that the chemotherapeutic drug and photothermal agent are synchronously delivered to a tumor area for their synergistic effect, dual‐target (RC‐12 and PG‐6 peptides) functionalized selenium nanoparticles loaded with both doxorubicin (DOX) and indocyanine green (ICG) were designed and successfully synthesized. The as‐synthesized nanoparticles exhibited good monodispersity, size stability, and consistent spectral characteristics compared with those of ICG or DOX alone. The nanoparticles underwent self‐immolated cleavage under irradiation from a near‐IR laser and released the loaded drug owing to sufficient hyperthermia. Moreover, the internalized nanoparticles triggered the overproduction of intracellular reactive oxygen species to induce cell apoptosis. Taken together, this study provides a sequentially triggered nanosystem to achieve precise drug delivery by chemo‐photothermal combination. [ABSTRACT FROM AUTHOR]

Abstract: A mutifunctional ruthenium‐based conjugate Ru‐BSe was designed and synthesized. The Ru complex with favorable bioimaging function was covalently linked with a cancer‐targeted molecule that could be effectively internalized by the tumor to realize enhanced theranostic effects. The pH‐response of the Ru conjugate in tumor acidic microenvironment causes ligand substitution and release of therapeutic complex. This activated complex remains inert to the reducing biomolecule‐glutathione and terminally locates in mitochondria, in which it triggers oxidative stress, and activates intrinsic apoptosis. Real‐time monitoring reveals that this Ru conjugate could selectively accumulate in tumor tissue in vivo, which significantly suppresses tumor progression and alleviate the damage to normal organs, realizing the precise cancer theranosis. [ABSTRACT FROM AUTHOR]

Cancer radiotherapy with 125I seeds demonstrates higher long-term efficacy and fewer side effects than traditional X-ray radiotherapy owing to its low-dose and continuous radiation but is still limited by radioresistance in clinical applications. Therefore, the design and synthesis of sensitizers that could enhance the sensitivity of cancer cells to 125I seeds is of great importance for future radiotherapy. Selenium nanoparticles (SeNPs) have been found to exhibit high potential in cancer chemotherapy and as drug carriers. In this study, we found that, based on the Auger-electron effect and Compton effect of Se atoms, cancer-targeted SeNPs in combination with 125I seeds achieve synergetic effects to inhibit cancer-cell growth and colony formation through the induction of cell apoptosis and cell cycle arrest. Detailed studies on the action mechanisms reveal that the combined treatments effectively activate intracellular reactive oxygen species (ROS) overproduction to regulate p53-mediated DNA damage apoptotic signaling pathways and mitogen-activated protein kinase (MAPK) phosphorylation and to prevent the self-repair of cancer cells simultaneously. Taken together, the combination of SeNPs with 125I seeds could be further exploited as a safe and effective strategy for next-generation cancer chemo-radiotherapy in clinical applications. [ABSTRACT FROM AUTHOR]

Antiangiogenesis therapy is a proven strategy for the treatment of cancers. Herein, we demonstrate that iron(II) complexes containing 1,10-phenanthroline(phen) derivatives were capable of suppressing angiogenesis in vitro in a dose-dependent manner. Interestingly, the introduction of selenium into an iron(II) complex ((Fe(phenSe)3(ClO4)2 (phenSe=2-selenoimidazole[4,5-f]1,10-phenanthroline)) could enhance its antiangiogenic efficacy. Mechanistic studies demonstrated that the complex potently induced endothelial cell apoptosis as evidenced by activation of caspases and PARP cleavage. The iron(II) complex activated p53-mediated mitochondrial dysfunction as can be seen by the upregulation in the expression of p53 and proapoptotic Bcl-2 family proteins, and downregulation in the expression of Bcl-2 family proteins. Additionally, the complex inhibited VEGF expression and gave rise to dephosphorylated AKT, which suppressed the transmission of the mitogenic signaling pathway. Taken together, this study could provide a strategy for the rational design of high-efficacy antivascular agents. [ABSTRACT FROM AUTHOR]

This study demonstrates a facile strategy by using chemically-synthesized lentinan-functionalized selenium nanoparticles (LNT-SeNPs) that could be simply obtained in large scale and display high antioxidative and anti-inflammatory activities to treat postoperative cognition dysfunction (POCD), and suggests that the use of translational LNT-SeNPs could be further developed as potent strategy for prevention and therapy of surgery-induced cognitive impairment. [Display omitted] • Our chemically-synthesized LNT-SeNPs that could be simply obtained in large scale. • LNT-SeNPs increased detoxifying selenoproteins in both serum and hippocampus. • LNT-SeNPs supplements significantly improved surgery-induced cognitive dysfunction. • LNT-SeNPs alleviated surgery-induced oxidative stress and neuroinflammation. • LNT-SeNPs also improved gut microbiome and intestinal barrier function. Postoperative cognition dysfunction (POCD) describes a condition of persistent deficits in attention, learning and memory following surgery. The mechanisms of POCD are far from being understood and the therapeutic strategies are limit. Surgery-induced oxidative stress and peripheral inflammation form a feedforward loop and eventually resulted in neuroinflammation, which underpin the pathogenesis of POCD. Therefore, the reactive oxygen species (ROS) homeostasis are tightly regulated by detoxifying enzymes, most of which are recognized as selenoproteins. The putative neuroprotective function of this trace element was investigated in this study using aged mice with POCD. Herein we demonstrate a facile strategy by using chemically-synthesized lentinan-functionalized selenium nanoparticles (LNT-SeNPs) that could be simply obtained in large scale and display high antioxidative and anti-inflammatory activities, to treat POCD. As expected, we found that, dietary supplements of LNT-SeNPs were effectively ingested and increased the levels of detoxifying selenoproteins in both serum and hippocampus of our aged mice. Behavioral assessments showed that LNT-SeNPs significantly improved the surgery-induced cognitive dysfunction, by alleviating surgery-induced oxidative stress and pro-inflammatory cytokine expression. In addition, dietary supplementation of LNT-SeNPs might protect central nervous system (CNS) function by improving gut microbiome and intestinal barrier function. Collectively, our results suggest that the use of translational LNT-SeNPs could be further developed as potent strategy for therapy of surgery-induced cognitive impairment. [ABSTRACT FROM AUTHOR]

Resistance of cancer to radiotherapy and/or chemotherapy is one of the important reasons of clinical treatment failure and recurrence. Chemoradiation is an optional method to over-coming of radioresistance and chemoresistance. Selenium nanoparticles (SeNPs) with special chemical and physical properties, has been identified as a novel nanocarrier and therapy agent with broad-spectrum anticancer activities due to generate ROS in cells. Herein, X-ray responsive selenium nanoparticles were facilely fabricated by using PEG as surface decorator and template. This nanosystem (PEG-SeNPs) demonstrated X-ray responsive property that was attributed to its amorphous characteristic. Interestingly, the nanosystem demonstrated significant radiosensitization effects with X-ray. Specifically, co-treatment of cancer cells with PEG-SeNPs and X-ray significantly and synergistically enhanced the cells growth inhibition through induction of cell apoptosis, as evidenced by DNA fragmentation and activation of caspase-3. In the cell model, we found that internalized nanoparticles could degrade upon X-ray exposure, which further confirm the X-ray responsive property of the nanoparticles. Moreover, the nanosystem could significantly induced intracellular ROS generation in a time-dependent manner, which peaked at about 40 min and gradually decreased thereafter. As a results, ROS overproduction led to mitochondria fragmentation and the cell apoptosis. Taken together, this study provides a novel strategy for rational design and facile synthesis of chemo-radio therapeutic radiosensitization nanomaterials. [ABSTRACT FROM AUTHOR]

Bone metastasis is the major cause of cancer-related morbidity and mortality. To avoid further osteolysis, current treatment ideas focus on tumor cell and the inhibition of osteoclast. Herein, zeolitic imidazolate framework-8–capped Cu 2-X Se composite nanoplatform (ICG@Cu 2-X Se-ZIF-8) is developed for chemodynamic therapy (CDT) and photothermal therapy (PTT) treatment of malignant breast cancer bone tumors. The rational design of ZIF-8 encapsulation greatly reduces the accumulation of Cu 2-X Se to damage the normal cells. Under acidic microenvironment in tumor, ZIF-8 is cleaved to release Cu 2-X Se, which can subsequently degrade into Cu (+) and Cu (2+) ions to initiate a Fenton-like reaction inducing CDT. Meanwhile, Cu 2-X Se is used to be an effective photothermal transduction agent for exerting the PTT effect. What's more, the selenium element in Cu 2-X Se can regulates selenoprotein to inhibit tumor cells and osteoclasts. Of note, the hyperthermia induced by PTT can further enhance the CDT effect in tumor, achieving a synergistic PTT/CDT effect. Based on these advantages, ICG@Cu 2-X Se-ZIF-8 effectively suppresses the tumor cells in bone tissue, and reduces the erosion of bone tissue via suppressing osteoclastogenesis. In conclusion, this study demonstrates the potential action mechanism of ZIF-8–capped nanomedicine against osteolysis in bone metastasis. [ABSTRACT FROM AUTHOR]

Herein a bioactive component of mannose-rich oligosaccharides with potent anti-inflammatory capacity was employed to functionalize SeNPs to achieve high stability, biocompatibility and therapeutic potential by promoting macrophages reprogramming leading to inflammation resolution. This study not only provides strategy for functionalization of nanomedicines using structure-optimized MRO, but also reveals the action mechanism on successful treatment of IBD and other intestinal diseases. [Display omitted] • Bioactive mannose-rich oligosaccharides were produced by enzymatic hydrolysis. • Functionalized MRO-SeNPs reprograms macrophage towards M2 polarization. • MRO-SeNPs effectively alleviates DSS-induced colitis in mice. Inflammatory bowel disease (IBD) is a global disease and usually classified into Crohn's disease (CD) and ulcerative colitis (UC), in which the inflammatory response is known to play a pivotal role. Herein, a bioactive component of mannose-rich oligosaccharides (MRO) was produced by enzymatic hydrolysis with most potent anti-inflammation and employed to functionalize selenium nanoparticles (SeNPs), aming to solve of inflammation in UC by accelerating the reprogramming of macrophages. In this study, SeNPs was prepared by selenite and MRO with ascorbic acid reduction. The stability and biocompatibility of SeNPs was obviously improved by the functionalization of MRO, resulting in spheres (2 µM Se) carrying around 26 ng/ml MRO (MRO-SeNPs) with an average diameter of 70 nm remained stable in 60 d. In addition, efficient cellular uptake of MRO-SeNPs in macrophages was detected by contribution of MRO targeted to the receptors of macrophages. As expected, MRO-SeNPs exhibited improvement of macrophage reprogramming in vitro , thus leading to a typical M2 polarization profile of cytokine expression. Furthermore, in DSS-induced mouse colitis model, MRO-SeNPs effectively mitigated colitis by suppressing the pro-inflammatory such as IL-1β, IL-6, TNF-α, IL-12 and MCP-1 cytokines in situ , and exerted salient antioxidant capacity in colon tissues. As a result, MRO-SeNPs exhibited therapeutic potential by promoting macrophages reprogramming leading to inflammation resolution. Taken together, this study not only provides strategy for functionalization of nanomedicines using structure-optimized MRO, but also reveals the action mechanism on successful treatment of IBD and other intestinal diseases. [ABSTRACT FROM AUTHOR]

A novel selenium-containing ruthenium complex Ru(phtpy)(phenSe)Cl(ClO4) (phtpy = 4-phenyl-2,2′:6′,2′′-terpyridine, phenSe = 2-selenicimidazole[4,5-f]1,10-phenanthroline) has been synthesized and found be able to enhance radiation-induced DNA damage through superoxide overproduction, which leads to G2/M arrest and apoptosis in cancer cells by activating ROS-mediated pathways. [ABSTRACT FROM AUTHOR]

Abstract: Selenium nanoparticles (SeNPs) have garnered a great deal of attention as potential cancer therapeutic payloads. However, the in vivo targeting drug delivery has been challenging. Herein, we describe the synthesis of tansferrin (Tf)-conjugated SeNPs and its use as a cancer-targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. Tf as targeting ligand significantly enhances the cellular uptake of doxorubicin (DOX)-loaded SeNPs through clathrin-mediated and caveolae/lipid raft-mediated endocytosis in cancer cells overexpressing transferrin receptor, and increases their selectivity between cancer and normal cells. DOX-loaded and Tf-conjugated SeNPs (Tf-SeNPs) exhibits unprecedented enhanced cytotoxicity toward cancer cells through induction of apoptosis with the involvement of intrinsic and extrinsic pathways. Internalized Tf-SeNPs triggers intracellular ROS overproduction, thus activates p53 and MAPKs pathways to promote cell apoptosis. In the nude mice xenograft experiment, Tf-SeNPs significantly inhibits the tumor growth via induction of p53-mediated apoptosis. This cancer-targeted design of SeNPs opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects. [Copyright &y& Elsevier]

Abstract: Although cisplatin is still one of the most effective chemotherapy agents for human cancers, its clinical use is limited by serious side effects, especially nephrotoxicity. Oxidative stress is an important mediator of cisplatin-induced nephrotoxicity. In the present study, a simple method for functionalization of selenium nanoparticles by self-assembly of 11-mercapto-1-undecanol (Se@MUN) to achieve enhanced antioxidant activity and antagonis against cisplatin-induced nephrotoxicity has been demonstrated. The chemical structure of the nanoparticles was characterized by various microscopic and spectroscopic methods. The results revealed that the spherical nanoparticles were capped with MUN on the surface through formation of Se-S bond. The in vitro protective effects of Se@MUN on HK-2 proximal tubular cells against cisplatin-induced nephrotoxicity and the underlying mechanisms were also investigated. Se@MUN exhibited free radical scavenging activity and higher cellular uptake in human normal cells by comparing with SeNPs. Se@MUN significantly attenuated cisplatin-induced reduction in cell viability, appearance of Sub-G1 peak, nuclear condensation and DNA fragmentation in HK-2 cells. Activation of caspase-3 in cells exposed to cisplatin was also effectively blocked by Se@MUN. Moreover, Se@MUN significantly prevented the cisplatin-induced overproduction of intracellular ROS. Our findings suggest that Se@MUN is a promising selenium species with potential application in prevention of cisplatin-induced renal injury. [Copyright &y& Elsevier]

Abstract: A simple method for fabrication of sialic acid surface-decorated selenium nanoparticles (SA–Se–NPs) with enhanced cancer-targeting and cell-penetrating abilities has been demonstrated in the present study. Monodisperse and homogeneous spherical SA–Se–NPs with striking stability were prepared under the optimized conditions. SA surface decoration significantly increased the cellular uptake and cytotoxicity of Se–NPs in HeLa human cervical carcinoma cells. Treatments of SA–Se–NPs induced dose-dependent apoptosis in HeLa cells, as evidenced by increase in sub-G1 cell populations, nuclear condensation and formation of apoptotic bodies. Further investigation on molecular mechanisms reveals that SA–Se–NPs triggered cancer cell apoptosis through activation of caspase-3 and subsequent cleavage of PARP. [Copyright &y& Elsevier]

Frontispiz: Chirality-Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles Keywords: Chiralität; Wirkstoffabgabe; Nanowirkstoffe; Selen-Nanopartikel Chiralität, Wirkstoffabgabe, Nanowirkstoffe, Selen-Nanopartikel. [Extracted from the article]

Developing safe, effective and targeting radiosensitizers with clear action mechanisms to achieve synergistic localized cancer treatment is an important strategy for radiotherapy. Herein, we design and synthesize a ternary heteronanostructure radiosensitizer (SeAuFe-EpC) with core/satellite morphology by a simple method to realize multimodal imaging-guided cancer radiotherapy. The mechanistic studies reveal that Se incorporation could drastically improve the electrical conductivity and lower the energy barrier between the three components, resulting in more electrons transfer between Se-Au interface and migration over the heterogeneous junction of Au-Fe 3 O 4 NPs interface. This synergistic interaction enhanced the energy transfer and facilitated more excited excitons generated by SeAuFe-EpC NPs, thus promoting the transformation of 3O 2 to 1O 2 via resonance energy transfer, finally resulting in irreversible cancer cell apoptosis. Additionally, based on the X-ray attenuation ability and high NIR absorption of AuNPs and the superparamagnetism of Fe 3 O 4 , in vivo computer tomography, photoacoustic and magnetic resonance tri-modal imaging have been employed to visualize the tracking and targeting ability of the NPs. As expected, the NPs specifically accumulated in orthotopic breast tumor area and achieved synergistic anticancer efficacy, but showed no toxic side effects on main organs. Collectively, this study sheds light on the potential roles of core/satellite heteronanostructure in imaging-guided cancer radiotherapy. Image 1 • A radiosensitive core/satellite heteronanostructure has been synthesized to achieve synergistic cancer radiotherapy. • Se incorporation could enhance energy transfer and facilitate more 1O 2 generation. • The radiosensitizer enables tri-modal imaging-guided cancer radiotherapy. [ABSTRACT FROM AUTHOR]

Immune cell therapy presents a paradigm for the treatment of malignant tumors. Human Vγ9Vδ2 T cells, a subset of peripheral γδ T cells, have been shown to have promising anti-tumor activity. However, new methodology on how to achieve a stronger anti-tumor activity of Vγ9Vδ2 T cells is under continuous investigation. In this work, we used selenium nanoparticles (SeNPs) to strengthen the anti-tumor cytotoxicity of Vγ9Vδ2 T cells. We found SeNPs pretreated γδ T cells had significantly stronger cancer killing and tumor growth inhibition efficacy when compared with γδ T cells alone. Simultaneously, SeNPs pretreatment could significantly upregulate the expression of cytotoxicity related molecules including NKG2D, CD16, and IFN-γ, meanwhile, downregulate PD-1 expression of γδ T cells. Importantly, we observed that SeNPs promoted tubulin acetylation modification in γδ T cells through interaction between microtubule network and lysosomes since the latter is the primary resident station of SeNPs shown by confocal visualization. In conclusion, SeNPs could significantly potentiate anti-tumor cytotoxicity of Vγ9Vδ2 T cells, and both cytotoxicity related molecules and tubulin acetylation were involved in fine-tuning γδ T cell toxicity against cancer cells. Our present work demonstrated a new strategy for further enhancing anti-tumor cytotoxicity of human Vγ9Vδ2 T cells by using SeNPs-based nanotechnology, not gene modification, implicating SeNPs-based nanotechnology had a promising clinical perspective in the γδ T cell immunotherapy for malignant tumors. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells-based therapy has been used widely for cancer treatment in clinic trails. However, the immunotherapeutic efficacy of this method has been greatly hindered by tumor evasion and diminished activities of NK cells. In the present study, a selenium (Se)-bearing ruthenium (Ru) complex (RuSe) was designed that could synergistically potentiate NK cell-mediated killing against prostate cancer cells. As expected, pretreatment of cancer cells with subtoxic doses of RuSe effectively augmented the lysis potency of NK cells, with up to 2.46-fold enhancement than NK cells alone, against PC3 cells. More importantly, low concentrations of RuSe could augment the tumor destroying potency of NK cells derived from 10 clinical patients, with the enhancement range from 0.78- to 11.9-fold against PC3 cells and 0.67- to 3.8-fold against LNCAP cells. Mechanistic studies revealed that the sensitizing effect of RuSe primarily depended on TRAIL/TRAIL-R and Fas/FasL-mediated signaling. Furthermore, the increased expression level of these ligands highly relied on ROS overproduction-triggered DNA damage and the downstream ATM and ATR pathways. Furthermore, RuSe potently activated and synergized with NK cells to restrain tumor growth in vivo without causing toxic side effects on major organs. Taken together, the current study not only provides a strategy for application of metal complexes in chemo-immunotherapy but also sheds light on the potential roles and mechanisms of action on such Se-containing drugs as efficient immune-sensitizing agents for NK cell-based immunotherapy. Findings show that Se-baring Ru complex could boost NK cells to treat prostate cancer via activating TRAIL- and FasL-mediated pathways, which not only provides a strategy for application of metal complexes in chemo-immunotherapy but also sheds light on the potential roles and action mechanisms of such Se-containing drug leads as efficient immune-sensitizing agents for NK cell-based immunotherapy. Image 1 [ABSTRACT FROM AUTHOR]

In this study, we synthesized a thermosensitive composite of Gel-SOR-LUF-SeNPs to achieve the localized synergistic chemoradiotherapy of hepatocellular carcinoma (HCC). Sorafenib (SOR) is one of the important clinical drugs for unresectable and advanced HCC. However, the uncontrollable release of SOR induced drug resistance and severe side effects. Recently, thermosensitive hydrogels have emerged as promising drug-delivery carriers, due to their superior advantages including biodegradability, low-toxicity, high drug loading, site-specificity, sustained and controlled drug release behavior. We synthesized the thermosensitive hydrogel nanosystem (Gel-SOR-LUF-SeNPs) as an effective drug release depot with the combination of radiotherapy for the localized and sustained treatment of HCC. The results showed that SOR was released continuously from Gel-SOR-LUF-SeNPs with the degradation of the hydrogel for a prolonged period (over 15 days). The combination of localized and chemoradiotherapy accelerated the apoptosis of HepG2 cells through reducing the expression of Ki67 and CD34, and activating caspase-3 signaling pathway. Further studies demonstrated that this nanosystem showed site-specific and long-term anticancer effects in mice up to 21 days after single subcutaneous injection, and no obvious side effects of mice were found. Taken together, this study presents a local and long-term treatment for HCC, which may shed light on unresectable HCC therapy in the future. Here, we reported a thermosensitive composite of Gel-SOR-LUF-SeNPs for the localized synergistic treatment of hepatocellular carcinoma (HCC). The composite was injected into HepG2 tumor-bearing nude mice in the state of solution to form hydrogel for long-acting therapy with the degradation of PLGA-PEG-PLGA. Image 1 [ABSTRACT FROM AUTHOR]

Apropos apoptosis: The introduction of selenium into an iron(II) complex could enhance its antiangiogenic efficacy by suppressing VEGF activation and AKT signaling pathway, and by activating p53 ‐ mediated mitochondrial dysfunction, thus leading to increased endothelial cell apoptosis. An underlying mechanism accounting for the angiogenesis inhibition effects has been proposed. More information can be found in the Communication by Tianfeng Chen et   al. on page   982 in Issue 9, 2017 (DOI: 10.1002/asia.201700272). [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) has attracted extensive interest for cancer treatment in the past years. In this study, chitosan (CS) ‐ modified Cu2Se nanoparticles (CS ‐ Cu2Se NPs) were synthesized with the aim to provide cancer chemotherapy and PTT. CS ‐ Cu2Se NPs were found to efficiently convert near ‐ infrared (NIR) light into heat and displayed excellent thermostability. Upon irradiation with a laser they effectively triggered overproduction of intracellular reactive oxygen species (ROS) that promoted cell apoptosis. Therefore, the as ‐ synthesized NPs may find use as anticancer agents for chemotherapy ‐ combined photothermal therapy. More information can be found in the Full Paper by Yan Bai, Tianfeng Chen et   al. on page   3032 in Issue 21, 2016 (DOI: 10.1002/asia.201600976). [ABSTRACT FROM AUTHOR]