Wide visible-range activatable fluorescence ZnSe:Eu3+/Mn2+@ZnS quantum dots: local atomic structure order and application as a nanoprobe for bioimaging.

The development of QDs-based fluorescent bionanoprobe for cellular imaging fundamentally relies upon the precise knowledge of particle-cell interaction, optical properties of QDs inside and outside of the cell, movement of a particle in and out of the cell, and the fate of particle. We reported engineering and physicochemical characterization of water-dispersible Eu3+/Mn2+ co-doped ZnSe@ZnS core/shell QDs and studied their potential as a bionanoprobe for biomedical applications, evaluating their biocompatibility, fluorescence behaviour by CytoViva dual mode fluorescence imaging, time-dependent uptake, endocytosis and exocytosis in RAW 264.7 macrophages. The oxidation state and local atomic structure of the Eu dopant studied by X-ray absorption fine structure (XAFS) analysis manifested that the Eu3+ ions occupied sites in both ZnSe and ZnS lattices for the core/shell QDs. A novel approach was developed to relieve the excitation constraint of wide bandgap ZnSe by co-incorporation of Eu3+/Mn2+ codopants, enabling the QDs to be excited at a wide UV-visible range. The QDs displayed tunable emission colors by a gradual increase in Eu3+ concentration at a fixed amount of Mn2+, systematically enhancing the Mn2+ emission intensity via energy transfer from the Eu3+ to Mn2+ ion. The ZnSe:Eu3+/Mn2+@ZnS QDs presented high cell viability above 85% and induced no cell activation. The detailed analyses of QDs-treated cells by dual mode fluorescence CytoViva microscopy confirmed the systematic color-tunable fluorescence and its intensity enhances as a function of incubation time. The QDs were internalized by the cells predominantly via macropinocytosis and other lipid raft-mediated endocytic pathways, retaining an efficient amount for 24 h. The unique color tunability and consistent high intensity emission make these QDs useful for developing a multiplex fluorescent bionanoprobe, activatable in wide-visible region.

Toxicological evaluation of 3-(4-Chlorophenylselanyl)-1-methyl-1H-indole through the bovine oocyte in vitro maturation model.

The development of new bioactive molecules based on the molecular hybridization has been widely explored. In line with this, reliable tests should be employed to give information about the toxicology of these new molecules. In this sense, the use of in vitro tests is a valuable tool, especially the in vitro maturation of oocytes (IVM), which is an efficient resource to discover the potential toxicity of synthetic molecules. Thus, the aim of the present study was to evaluate the toxicological effects of the selenium-containing indolyl compound 3-(4-Chlorophenylselanyl)-1-methyl-1H-indole (CMI), on different quality parameters of bovine oocytes through the IVM. Different concentrations of the CMI compound (0, 25, 50, 100, 200 µM) were supplemented during the in vitro maturation process. After, the oocyte maturation rate, glutathione (GSH) levels, reactive oxygen species (ROS) levels, membrane, and mitochondrial integrity were evaluated. The results showed that the lowest concentration of CMI induced the highest GSH production (P < 0.05), an important marker of cytoplasmic quality and maturation. All treatments increased ROS production in relation to non-supplementation (P < 0.05). In addition, oocyte maturation was reduced only with the highest concentration of CMI (P < 0.05). Supplementation with CMI did not impact mitochondrial activity, integrity and cell membrane. To our knowledge, this is the first study that evaluates CMI on the oocyte in vitro maturation process. Importantly, our results did not find any toxic effect of CMI on bovine oocytes. CMI was efficient for cytoplasmic maturation by promoting an increase in the intracellular levels of glutathione.

Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice.

Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.

Selenoxides inhibit delta-aminolevulinic acid dehydratase.

The effect of two selenides and their selenoxides on delta-aminolevulinic acid dehydratase (delta-ALA-D) from liver of adult rats was investigated. In vivo, selenides can be oxidized to selenoxides by flavin-containing monooxygenases (FMO) and selenoxides can regenerate selenides by thiol oxidation. Phenyl methyl selenide (PhSeCH3) and 1-hexynyl methyl selenide (C4H9Ctriple bondCSeCH3) were converted to selenoxides by reaction with H2O2. PhSeCH3 and C4H9Ctriple bondCSeCH3 had no effect on delta-ALA-D up to 400 microM. Conversely, their selenoxides inhibited delta-ALA-D, and the IC(50) for enzyme inhibition was about 100 and 70 microM, respectively. Partially purified delta-ALA-D (P(55)) from swine liver was also inhibited by these selenoxides. The inhibitory action of selenoxides was antagonized by dithiotreitol (DTT). Moreover, delta-ALA-D from a plant source was inhibited by the selenoxides, suggesting a possible involvement of SH groups in a distinct site of the homologous region implicated in Zn2+ binding in mammalian delta-ALA-D. After exposure to PhSeCH3 (500 micromol/kg/day) for 45 or 30 days, the activity of delta-ALA-D from liver of mice decreased to about 50% of the control group. The in vivo inhibitory action of this compound was not antagonized by DTT. PhSeCH3 and C4H9Ctriple bondCSeCH3 had no effect on the rate of DTT oxidation, but their selenoxides oxidized DTT. The results of the present study suggest that hepatic delta-ALA-D of rodents is a potential molecular target for selenides as a consequence of their metabolism to selenoxides by FMO.