Sepsis,a life-threatening syndrome of organ damage resulting from dysregulated inflammatory response,is distinguished by overexpression of inflammatory cytokines,excessive generation of reactive oxygen/nitrogen specie...Sepsis,a life-threatening syndrome of organ damage resulting from dysregulated inflammatory response,is distinguished by overexpression of inflammatory cytokines,excessive generation of reactive oxygen/nitrogen species(RONS),heightened activation of pyroptosis,and suppression of autophagy.However,current clinical symptomatic supportive treatment has failed to reduce the high mortality.Herein,we developed self-assembled multifunctional carbon monoxide nanogenerators(Nano CO),as sepsis drug candidates,which can release CO in response to ROS,resulting in clearing bacteria and activating the heme oxygenase-1/CO system.This activation strengthened endogenous protection and scavenged multiple inflammatory mediators to alleviate the cytokine storm,including scavenging RONS and cfDNA,inhibiting macrophage activation,blocking pyroptosis and activating autophagy.Animal experiments show that Nano CO has a good therapeutic effect on mice with LPSinduced sepsis,which is manifested in hypothermia recovery,organ damage repair,and a 50%decrease in mortality rates.Taken together,these results illustrated the efficacy of multifunctional Nano CO to target clearance of multiple mediators in sepsis treatment and act against other refractory inflammation-related diseases.展开更多
基金supported by National Natural Science Foundation of China(Grant No.82302720 to Y.Wu,82125023,82072504 to H.Xie,82272562 to Z-X Wang),Natural Science Foundation of Hunan Province(Grant No.2023JJ40997 to Y.Wu)China Postdoctoral Science Foundation(Grant No.2023M733964 to Y.Wu,2023M733946 to X.Chen).
文摘Sepsis,a life-threatening syndrome of organ damage resulting from dysregulated inflammatory response,is distinguished by overexpression of inflammatory cytokines,excessive generation of reactive oxygen/nitrogen species(RONS),heightened activation of pyroptosis,and suppression of autophagy.However,current clinical symptomatic supportive treatment has failed to reduce the high mortality.Herein,we developed self-assembled multifunctional carbon monoxide nanogenerators(Nano CO),as sepsis drug candidates,which can release CO in response to ROS,resulting in clearing bacteria and activating the heme oxygenase-1/CO system.This activation strengthened endogenous protection and scavenged multiple inflammatory mediators to alleviate the cytokine storm,including scavenging RONS and cfDNA,inhibiting macrophage activation,blocking pyroptosis and activating autophagy.Animal experiments show that Nano CO has a good therapeutic effect on mice with LPSinduced sepsis,which is manifested in hypothermia recovery,organ damage repair,and a 50%decrease in mortality rates.Taken together,these results illustrated the efficacy of multifunctional Nano CO to target clearance of multiple mediators in sepsis treatment and act against other refractory inflammation-related diseases.
