Rapid development of checkpoint inhibitors has provided significant breakthroughs for cancer stem cell(CSC)therapy,while the therapeutic efficacy is restricted by hypoxia-mediated tumor immune evasion,especially hypox...Rapid development of checkpoint inhibitors has provided significant breakthroughs for cancer stem cell(CSC)therapy,while the therapeutic efficacy is restricted by hypoxia-mediated tumor immune evasion,especially hypoxia-induced CD47 overexpression in CSCs.Herein,we developed a genetically engineered CSC membrane-coated hollow manganese dioxide(hMnO_(2)@gCMs)to elicit robust antitumor immunity by blocking CD47 and alleviating hypoxia to ultimately achieve the eradication of CSCs.The hMnO_(2)core effectively alleviated tumor hypoxia by inducing decomposition of tumor endogenous H_(2)O_(2),thus suppressing the CSCs and reducing the expression of CD47.Cooperating with hypoxia relief-induced downregulation of CD47,the overexpressed SIRPαon gCM shell efficiently blocked the CD47-SIRPα“don’t eat me”pathway,synergistically eliciting robust antitumor-mediated immune responses.In a B16F10-CSC bearing melanoma mouse model,the hMnO_(2)@gCMs showed an enhanced therapeutic effect in eradicating CSCs and inhibiting tumor growth.Our work presents a simple,safe,and robust platform for CSC eradication and cancer immunotherapy.展开更多
The hydrogenation of CO_(2)to methanol,which is restricted by water products,requires a selective removal of water from the reaction system.Here,we show that physically combining hydrophobic polydivinylbenzene with a ...The hydrogenation of CO_(2)to methanol,which is restricted by water products,requires a selective removal of water from the reaction system.Here,we show that physically combining hydrophobic polydivinylbenzene with a copper catalyst supported by silica can increase methanol production and CO_(2)conversion.Mechanistic investigation reveals that the hydrophobic promoter could hinder the oxidation of copper surface by water,maintaining a small fraction of metallic copper species on the copper surface with abundant Cu^(δ+),resulting in high activity for the hydrogenation.Such a physically mixed catalyst survives the continuous test for 100 h owing to the thermal stability of the polydivinylbenzene promoter.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82222035 and 82372106)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515110633)+2 种基金the Shenzhen Medical Research Found(No.B2302041)the Shenzhen Science and Technology Program(No.RCBS20221008093123060)the Shenzhen Bay Laboratory Proof-of-Concept Fund(No.S231801005).
文摘Rapid development of checkpoint inhibitors has provided significant breakthroughs for cancer stem cell(CSC)therapy,while the therapeutic efficacy is restricted by hypoxia-mediated tumor immune evasion,especially hypoxia-induced CD47 overexpression in CSCs.Herein,we developed a genetically engineered CSC membrane-coated hollow manganese dioxide(hMnO_(2)@gCMs)to elicit robust antitumor immunity by blocking CD47 and alleviating hypoxia to ultimately achieve the eradication of CSCs.The hMnO_(2)core effectively alleviated tumor hypoxia by inducing decomposition of tumor endogenous H_(2)O_(2),thus suppressing the CSCs and reducing the expression of CD47.Cooperating with hypoxia relief-induced downregulation of CD47,the overexpressed SIRPαon gCM shell efficiently blocked the CD47-SIRPα“don’t eat me”pathway,synergistically eliciting robust antitumor-mediated immune responses.In a B16F10-CSC bearing melanoma mouse model,the hMnO_(2)@gCMs showed an enhanced therapeutic effect in eradicating CSCs and inhibiting tumor growth.Our work presents a simple,safe,and robust platform for CSC eradication and cancer immunotherapy.
基金supported by the National Key Research and Development Program of China(2022YFA1503502)the National Natural Science Foundation of China(22288101,22241801,U21B20101,and 22102142).
文摘The hydrogenation of CO_(2)to methanol,which is restricted by water products,requires a selective removal of water from the reaction system.Here,we show that physically combining hydrophobic polydivinylbenzene with a copper catalyst supported by silica can increase methanol production and CO_(2)conversion.Mechanistic investigation reveals that the hydrophobic promoter could hinder the oxidation of copper surface by water,maintaining a small fraction of metallic copper species on the copper surface with abundant Cu^(δ+),resulting in high activity for the hydrogenation.Such a physically mixed catalyst survives the continuous test for 100 h owing to the thermal stability of the polydivinylbenzene promoter.
