An infection-microenvironment-targeted and responsive peptide-drug nanosystem for sepsis emergency by suppressing infection and inflammation

作     者：Wei He Daan Fu Yongkang Gai Xingxin Liu Chang Yang Zhilan Ye Xu Chen Jia Liu Bingcheng Chang Wei He;Daan Fu;Yongkang Gai;Xingxin Liu;Chang Yang;Zhilan Ye;Xu Chen;Jia Liu;Bingcheng Chang

作者机构：The Second Clinical CollegeThe Second Affiliated HospitalGuizhou University of Traditional Chinese MedicineGuiyang 550003China Research Center for Tissue Engineering and Regenerative MedicineTongji Medical CollegeUnion HospitalHuazhong University of Science and TechnologyWuhan 430022China Department of AnesthesiologyTongji Medical CollegeUnion HospitalHuazhong University of Science and TechnologyWuhan 430022China Department of Laboratory MedicineWest China Second University HospitalSichuan UniversityChengdu 610065China Department of Nuclear MedicineHubei Province Key Laboratory of Molecular ImagingTongji Medical CollegeUnion HospitalHuazhong University of Science and TechnologyWuhan 430022China Guizhou Provincial Key Laboratory of PharmaceuticsGuizhou Medical UniversityGuiyang 550004China Department of GeriatricsTongji Medical CollegeUnion HospitalHuazhong University of Science and TechnologyWuhan 430022China 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2023年第18卷第6期

页      面：126-143页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：supported by the Program of the Scientific and Technological in Guiyang City(Grant No.Zhu Ke He-16-5) Program of Scientific and Technological Project in Guizhou Province(Grant No.4Y197,Qian Ke He Ji Chu ZKYi Ban 516,Qian Ke He Ji Chu ZKYi Ban 559) the Science and Technology Talents Growth Project in Education Department of Guizhou Province(Grant No.Qian Jiao He KY Zi4Y211) the Program of Science and Technology of Guizhou Provincial Health Commission(Grant No.gzwjkj2020-1-215) the Knowledge Innovation Special Project for Fundamental Research of Wuhan(Grant No.2022020801010461) the Sichuan Science and Technology Program(Grant No.2022NSFSC1420) 

主　　题：Infectious microenvironments Sepsis Nanoscale drug delivery systems Pathogens Omiganan 

摘      要：Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and ***,current therapeutic regimens are inadequate to promptly address the vast diversity of potential ***,an antimicrobial peptide,has shown promise for neutralizing endotoxins and eliminating diverse ***,its clinical application is hindered by safety and stability ***,we present a nanoscale drug delivery system(Omi-hyd-Dex@HA NPs)that selectively targets infectious microenvironments(IMEs)and responds to specific stimuli for efficient intervention in *** system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid(HA).The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes,but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by *** nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress *** multiple tissue infection and sepsis animal models,Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction,thereby preventing subsequent fatal complications and significantly improving survival *** bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.