生物膜
中性粒细胞胞外陷阱
免疫系统
微生物学
吞噬作用
活性氧
生物
细胞生物学
髓过氧化物酶
免疫学
炎症
细菌
遗传学
作者
Geyong Guo,Zihao Liu,Jinlong Yu,Yanan You,Mingzhang Li,Boyong Wang,Jin Tang,Pei Han,Jianrong Wu,Hao Shen
标识
DOI:10.1002/adma.202310320
摘要
Abstract Reinforced biofilm structures and dysfunctional neutrophils induced by excessive oxidative stress contribute to the refractoriness of diabetes‐related biofilm infections (DRBIs). Herein, in contrast to traditional antibacterial therapies, an immune switchpoint‐driven neutrophil immune function conversion strategy based on a deoxyribonuclease I loaded vanadium carbide MXene (DNase‐I@V 2 C) nanoregulator is proposed to treat DRBIs via biofilm lysis and redirecting neutrophil functions from NETosis to phagocytosis in diabetes. Owing to its intrinsic superoxide dismutase/catalase‐like activities, DNase‐I@V 2 C effectively scavenges reactive oxygen species (ROS) in a high oxidative stress microenvironment to maintain the biological activity of DNase‐I. By increasing the depth of biofilm penetration of DNase‐I, DNase‐I@V 2 C thoroughly degrades extracellular DNA and neutrophil extracellular traps (NETs) in extracellular polymeric substances, thus breaking the physical barrier of biofilms. More importantly, as an immune switchpoint regulator, DNase‐I@V 2 C can skew neutrophil functions from NETosis toward phagocytosis by intercepting ROS–NE/MPO–PAD4 and activating ROS–PI3K–AKT–mTOR pathways in diabetic microenvironment, thereby eliminating biofilm infections. Biofilm lysis and synergistic neutrophil function conversion exert favorable therapeutic effects on biofilm infections in vitro and in vivo. This study serves as a proof‐of‐principle demonstration of effectively achieving DRBIs with high therapeutic efficacy by regulating immune switchpoint to reverse neutrophil functions.
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