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 tumo...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.展开更多
Plant viruses cause symptoms with devastating consequences for agriculture.However,the molecular mechanisms underlying symptom development in viral infections remain largely unexplored.Here,we show that tomato yellow ...Plant viruses cause symptoms with devastating consequences for agriculture.However,the molecular mechanisms underlying symptom development in viral infections remain largely unexplored.Here,we show that tomato yellow leaf curl virus(TYLCV)interferes with host developmental programs through a host-mimicking domain present in the viral C4 protein.This domain mediates the interaction between C4 and a family of RCC1-like domain-containing(RLD)proteins,previously shown to be required for proper plant development and environmental responses.C4 outcompetes an endogenous interactor of RLDs,hijacking RLD proteins to the plasma membrane and disrupting their function in orchestrating endomembrane trafficking and polar auxin transport.Strikingly,macroscopic symptoms do not affect viral accumulation in the plant but serve as attractants for the insect vector,presumably promoting pathogen spread in an ecological context.Our work sheds light on the molecular underpinnings and biological relevance of symptom development triggered by TYLCV in tomato.Since most plant viruses are insect-transmitted,the principles described here might have broad applicability to crop-virus interactions.展开更多
Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for...Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic.The multifunctional probes consisted of a gold/platinum star-shaped core(Au/Pt star)conjugated with a GSH-sensitive disulfide bond(S–S),a targeting ligand(rHSA-FA),a near-infrared fluorophore(IR780)and glucose oxidase(GOx).When systemically administered in a xenografted murine model,the probes specifically targeted the tumor sites.As the disulfide linker was cleaved by intracellular GSH,the IR780 molecules could be released for photo-thermal therapy&photodynamic therapy(PTT&PDT)and imaging.Subsequently,the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system:GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity,and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic·OH for tumor oxidative damage.Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release,real-time imaging ability,and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features,which provides a potential strategy for effective tumor theragnostic.展开更多
基金supported from 973 Project (Grant No. 2015CB931802 and 2017YFA0205301)Chinese National Natural Scientific Fund (Grant No.81327002 and 81803094)+1 种基金China Postdoctoral Science Foundation (Grant No. 2017M621486)Funding from Shanghai Engineering Research Center for Intelligent diagnosis and treatment instrument (Grant No.15DZ2252000)
文摘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.
基金funded by the Excellence Strategy of the German Federal and State Governments,the ERC-COG GemOmics(101044142)the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)(project numbers TRR 356/1,B04 and SBF 1101/3,C08)+3 种基金a Royal Society Newton Advance Grant(NA140481-NAF\R2\180857)Metabolite analytics were funded by the DFG(Projektnummer 442641014)the recipient of a Marie Skłodowska-Curie Grant from the European Union’s Horizon 2020 Research and Innovation Program(grant 896910-GeminiDECODER)a President’s International Fellowship Initiative(PIFI)from the Chinese Academy of Science(CAS)(grant 2020PB0082).
文摘Plant viruses cause symptoms with devastating consequences for agriculture.However,the molecular mechanisms underlying symptom development in viral infections remain largely unexplored.Here,we show that tomato yellow leaf curl virus(TYLCV)interferes with host developmental programs through a host-mimicking domain present in the viral C4 protein.This domain mediates the interaction between C4 and a family of RCC1-like domain-containing(RLD)proteins,previously shown to be required for proper plant development and environmental responses.C4 outcompetes an endogenous interactor of RLDs,hijacking RLD proteins to the plasma membrane and disrupting their function in orchestrating endomembrane trafficking and polar auxin transport.Strikingly,macroscopic symptoms do not affect viral accumulation in the plant but serve as attractants for the insect vector,presumably promoting pathogen spread in an ecological context.Our work sheds light on the molecular underpinnings and biological relevance of symptom development triggered by TYLCV in tomato.Since most plant viruses are insect-transmitted,the principles described here might have broad applicability to crop-virus interactions.
基金support of the National Basic Research Program of China(Nos.2017YFA0205301 and 2015CB931802)the National Natural Scientific Foundation of China(Nos.81903169,81803094,81602184,81822024,and 81571729)+5 种基金Shanghai Municipal Commission of Economy and Information Technology Fund(No.XC-ZXSJ-02-2016-05)the Medical Engineering Cross Project of Shanghai Jiao Tong university(Nos.YG2016ZD10 and YG2017Z D05)the Project of Thousand Youth Talents from China,and the National Key Research and Development Program of China(No.2017YFC1200904)the financial support of Shanghai Sailing Program(No.19YF1422300)Sponsor from Startup Fund for Yongman Research at SJTU(No.18X100040044)Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument(No.15DZ2252000)are also acknowledged.
文摘Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic.The multifunctional probes consisted of a gold/platinum star-shaped core(Au/Pt star)conjugated with a GSH-sensitive disulfide bond(S–S),a targeting ligand(rHSA-FA),a near-infrared fluorophore(IR780)and glucose oxidase(GOx).When systemically administered in a xenografted murine model,the probes specifically targeted the tumor sites.As the disulfide linker was cleaved by intracellular GSH,the IR780 molecules could be released for photo-thermal therapy&photodynamic therapy(PTT&PDT)and imaging.Subsequently,the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system:GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity,and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic·OH for tumor oxidative damage.Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release,real-time imaging ability,and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features,which provides a potential strategy for effective tumor theragnostic.
