Translational Selenium Nanoparticles to Attenuate Allergic Dermatitis through Nrf2-Keap1-Driven Activation of Selenoproteins.

Easy recurrence and strong treatment side effects significantly limit the clinical treatment of allergic dermatitis. The human trace element selenium (Se) plays essential roles in redox regulation through incorporation into selenoproteins in the form of 21st necessary amino acid selenocysteine, to participates in the pathogenesis and intervention of chronic inflammatory diseases. Therefore, based on the safe and elemental properties of Se, we construct a facile-synthesis strategy for antiallergic selenium nanoparticles (LET-SeNPs), and scale up the production by employing a spray drying method with lactose (Lac-LET-SeNPs) or maltodextrin (Mal-LET-SeNPs) as encapsulation agents realizing larger scale production and a longer storage time. As expected, these as-prepared LET-SeNPs could effectively activate the Nrf2-Keap1 signaling pathway to enhance the expression of antioxidative selenoprotein at mRNA and protein levels, then inhibit mast cell activation to achieve efficient antiallergic activity. Interestingly, LET-SeNPs undergo metabolism to seleno-amino acids to promote biosynthesis of selenoproteins, which could suppress ROS-induced cyclooxygenase-2 (COX-2) and MAPKs activation to suppress the release of histamine and inflammatory cytokines. Allergic mouse and Macaca fascicularis models further confirm that LET-SeNPs could increase the Se content and selenoprotein expression in the skin, decrease mast cells activation and inflammatory cells infiltration, and finally exhibit the high therapeutic effects on allergic dermatitis. Taken together, this study not only constructs facile large-scale synthesis of translational Se nanomedicine to break through the bottleneck problem of nanomaterials but also sheds light on its application in the intervention and treatment of allergies.

Selenium-containing ruthenium complex synergizes with natural killer cells to enhance immunotherapy against prostate cancer via activating TRAIL/FasL signaling.

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.

Potentiation of in Vivo Anticancer Efficacy of Selenium Nanoparticles by Mushroom Polysaccharides Surface Decoration.

Selenium nanoparticles (SeNPs) are recently emerging as promising anticancer agents because of their high bioavailability, low toxicity and remarkable anticancer activities. However, the effects of surface physicochemical properties on the biological actions remain elusive. Herein we decorated SeNPs with various water-soluble polysaccharides extracted from various mushrooms, to compare physical characteristics and anticancer profile of these SeNPs. The results showed that the prepared spherical SeNPs displayed particle sizes at 91-102 nm, and kept stable in aqueous solution for up to 13 weeks. However, different decoration altered the tumor selectivity of the SeNPs, while gastric adenocarcinoma AGS cells showed relative highest sensitivity. Moreover, PTR-SeNPs demonstrated potent in vivo antitumor, by inducing caspases- and mitochondria-mediated apoptosis, but showed no obvious toxicity to nomal organs. Taken together, this study offers insights into how surface decoration can tune the cancer selectivity of SeNPs and provides a basis for engineering particles with increased anticancer efficacy.