The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment(TME)and inferior drug targeting.Herein,an active targeting TM...The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment(TME)and inferior drug targeting.Herein,an active targeting TME nanoplatform capable of revising the immunosuppressive TME microenvironment is designed.Briefly,gold nanorods(GNRs)are covered with silica dioxide(SiO_(2))and then coated manganese dioxide(MnO_(2))to obtain GNRs@SiO_(2)@MnO_(2)(GSM).Myeloid-derived suppressor cells(MDSCs)membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO_(2)@MnO_(2)@MDSCs(GSMM).In this system,GSMM inherits active targeting TME capacity of MDSCs.The localized surface plasmon resonance of GNRs is developed in near-infraredⅡwindow by MnO_(2)layer coating,realizing NIR-Ⅱwindow photothermal imaging and photoacoustic imaging of GSMM.Based on the release of Mn^(2+)in acidic TME,GSMM can be also used for magnetic resonance imaging.In cancer cells,Mn^(2+)catalyzes H_(2)O_(2)into·OH for(chemodynamic therapy)CDT leading to activate cGAS-STING,but also directly acts on STING inducing secretion of typeⅠinterferons,pro-inflammatory cytokines and chemokines.Additionally,photothermal therapy and CDT-mediated immunogenic cell death of tumor cells can further enhance anti-tumor immunity via exposure of CRT,HMGB1 and ATP.In summary,our nanoplatform realizes multimodal cancer imaging and dual immunotherapy.展开更多
基金financial support from National Natural Science Foundation of China(82103404)Guangdong Basic and Applied Basic Research Foundation(2020A1515110719)+4 种基金Southern Medical University Excellent Youth Scholars Training Program(2020YQPY008)Guangzhou Basic and Applied Basic Research Foundation(202102020687)Stomatological Hospital of Southern Medical University Startup Funds(No.PY2020001,PY2019026)High-level Hospital Construction Project(KJ012019100)Shenzhen Bay Laboratory Startup Fund(No.21310071).
文摘The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment(TME)and inferior drug targeting.Herein,an active targeting TME nanoplatform capable of revising the immunosuppressive TME microenvironment is designed.Briefly,gold nanorods(GNRs)are covered with silica dioxide(SiO_(2))and then coated manganese dioxide(MnO_(2))to obtain GNRs@SiO_(2)@MnO_(2)(GSM).Myeloid-derived suppressor cells(MDSCs)membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO_(2)@MnO_(2)@MDSCs(GSMM).In this system,GSMM inherits active targeting TME capacity of MDSCs.The localized surface plasmon resonance of GNRs is developed in near-infraredⅡwindow by MnO_(2)layer coating,realizing NIR-Ⅱwindow photothermal imaging and photoacoustic imaging of GSMM.Based on the release of Mn^(2+)in acidic TME,GSMM can be also used for magnetic resonance imaging.In cancer cells,Mn^(2+)catalyzes H_(2)O_(2)into·OH for(chemodynamic therapy)CDT leading to activate cGAS-STING,but also directly acts on STING inducing secretion of typeⅠinterferons,pro-inflammatory cytokines and chemokines.Additionally,photothermal therapy and CDT-mediated immunogenic cell death of tumor cells can further enhance anti-tumor immunity via exposure of CRT,HMGB1 and ATP.In summary,our nanoplatform realizes multimodal cancer imaging and dual immunotherapy.
