Neutrophil Function Conversion Driven by Immune Switchpoint Regulator against Diabetes-Related Biofilm Infections
© 2023 Wiley-VCH GmbH.
Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 8 vom: 01. Feb., Seite e2310320 |
---|---|
1. Verfasser: | |
Weitere Verfasser: | , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2024
|
Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
Schlagworte: | Journal Article DNase-I diabetes-related biofilm infections immune switchpoint neutrophil extracellular traps phagocytosis Reactive Oxygen Species Phosphatidylinositol 3-Kinases EC 2.7.1.- Deoxyribonucleases |
Zusammenfassung: | © 2023 Wiley-VCH GmbH. 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-IV2 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@V2 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@V2 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@V2 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 |
---|---|
Beschreibung: | Date Completed 23.02.2024 Date Revised 23.02.2024 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-4095 |
DOI: | 10.1002/adma.202310320 |