Human natural killer cells for targeting delivery of gold nanostars and bimodal imaging directed photothermal/photodynamic therapy and immunotherapy

Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumor targeted therapy.Methods:GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis.The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry(FCM)and ELISA.Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8.Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic(CLSM)and FCM at different time points.Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM.The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging.The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.Results:The coated CaC03 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.Conclusions:The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice.Through fully utilizing the features of GNSs and NK cells,this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.

C60 Fullerenes Suppress Reactive Oxygen Species Toxicity Damage in Boar Sperm

We report the carboxylated C60 improved the survival and quality of boar sperm during liquid storage at 4°C and thus propose the use of carboxylated C60 as a novel antioxidant semen extender supplement.Our results demonstrated that the sperm treated with 2μg mL?1 carboxylated C60 had higher motility than the control group(58.6%and 35.4%,respectively;P?0.05).Moreover,after incubation with carboxylated C60 for 10 days,acrosome integrity and mitochondrial activity of sperm increased by 18.1%and 34%,respectively,compared with that in the control group.Similarly,the antioxidation abilities and adenosine triphosphate levels in boar sperm treated with carboxylated C60 significantly increased(P?0.05)compared with those in the control group.The presence of carboxylated C60 in semen extender increases sperm motility probably by suppressing reactive oxygen species(ROS)toxicity damage.Interestingly,carboxylated C60 could protect boar sperm from oxidative stress and energy deficiency by inhibiting the ROS-induced protein dephosphorylation via the cAMP-PKA signaling pathway.In addition,the safety of carboxylated C60 as an alternative antioxidant was also comprehensively evaluated by assessing the mean litter size and number of live offspring in the carboxylated C60 treatment group.Our findings confirm carboxylated C60 as a novel antioxidant agent and suggest its use as a semen extender supplement for assisted reproductive technology in domestic animals.

从探秘到保护:纪实影像中西藏乡土形象变迁

中国共产党历来重视民族文化事业的发展。1951年西藏解放以来,大量的纪实影像记录了当地的乡土形象变迁。通过对近年来影像文本的内容分析发现,西藏题材纪录片中对于乡村图景的表达大体呈现了从“文化探秘”到“文化保护”的转向。价值和叙事策略转向下的西藏题材纪录片更加重视人本主义、追求文化发展的可持续性、注重对生活美学的展现,重塑了西藏的媒介形象。