Pulmonary Delivery of siRNA Anti-TNFα-loaded Lipid Nanoparticles for Rapid Recovery in Murine Acute Lung Injury.

ABSTRACT: This study investigates the potential of pulmonary delivery of siRNA as an emergency therapy for acute lung injury (ALI). To obtain a quick anti-inflammatory response, TNF-α, a critical pro-inflammatory cytokine, is knocked down for its early involvement in inflammatory responses. Therefore, TNF-α siRNA-lipid nanoparticles (LNPs) are designed and characterized for cellular uptake in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophages, primary alveolar macrophages, and neutrophils from a murine ALI model. Intracellular trafficking and siRNA cytoplasmic release are evaluated in untreated and LPS-activated RAW264.7 cells. LPS-activated cells exhibit a fast and strong uptake of LNPs, including in primary cells. In RAW264.7 cells, significant endosomal escape and siRNA cytoplasmic re

SUBMITTER: Wang Q 

PROVIDER: S-EPMC12616584 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature