Targeted inhibition of PARP-1 in pulmonary epithelial cells and macrophages via SPA-functionalized microparticles attenuates sepsis-induced lung injury - PubMed
14 hours ago
- #Sepsis
- #Targeted drug delivery
- #PARP-1 inhibition
- Sepsis-induced acute lung injury (ALI) is a life-threatening condition with limited therapeutic options.
- Hyperactivation of PARP-1 is a key contributor to inflammation and cellular injury in sepsis.
- Pulmonary epithelial cells and macrophages were identified as major pro-inflammatory hubs in the septic lung.
- A lung-targeted nanotherapeutic was developed by encapsulating PARP-1 inhibitor olaparib into SPA-functionalized microparticles (OLA@SPA MPs).
- OLA@SPA MPs showed enhanced pulmonary accumulation and efficient internalization by target cells, suppressing PARP-1 activation.
- In murine sepsis models, OLA@SPA MPs reduced vascular leakage, modulated cytokine storm, attenuated lung damage, and improved survival.
- Transcriptomic analyses revealed OLA@SPA MPs downregulated pro-inflammatory pathways like NOD-like receptor and TNF signaling.
- This study presents a targeted therapeutic approach for sepsis-induced lung injury.