Back to Search
Start Over
The delivery of PD-L1 siRNA by neutrophil-targeted lipid nanoparticles effectively ameliorates sepsis.
- Source :
-
Shock (Augusta, Ga.) [Shock] 2024 Aug 12. Date of Electronic Publication: 2024 Aug 12. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- Background: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo.<br />Methods: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture (CLP) model was used to detect neutrophil migration, neutrophil extracellular traps (NETs) level, and organ damage.<br />Result: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of NETs, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multi-organ damage and lethality resulting from CLP.<br />Conclusions: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy.<br /> (Copyright © 2024 by the Shock Society.)
Details
- Language :
- English
- ISSN :
- 1540-0514
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 39158541
- Full Text :
- https://doi.org/10.1097/SHK.0000000000002450