Self-assembled carbon monoxide nanogenerators managing sepsis through scavenging multiple inflammatory mediators  

作　　者：Yang Wu Xia Chen Zhaolin Zeng Bei Chen Zhenxing Wang Zhiyong Song Hui Xie 

机构地区：[1]Department of Orthopedics,Movement System Injury and Repair Research Center,Xiangya Hospital,Central South University,Changsh1,Hunan,410008,China [2]Hunan Key Laboratory ofÅngmedicine,Xiangya Hospital,Central South University,Changsh1,Hunan,410008,China [3]National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsh1,Hunan,410008,China [4]Department of Clinical Laboratory,Xiangya Hospital,Central South University,Changsh1,Hunan,410008,China [5]Department of Metabolism and Endocrinology,The First Affiliated Hospital,Hengyang Medical School,University of South Chin1,Hengyang,Hunan,421001,China [6]State Key Laboratory of Agriculture Microbiology,College of Science,Huazhong Agricultural University,Wuhan,Hubei,430070,China

出　　处：《Bioactive Materials》2024年第9期595-611,共17页生物活性材料（英文）

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).

摘　　要：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.

关 键 词：SEPSIS Carbon monoxide nanogenerator Heme oxygenase-1 Scavenging inflammatory storm 

分 类 号：R515.3[医药卫生—内科学]