Abstract
Acute lung injury (ALI) is a devastating clinical syndrome causing a substantial mortality, but to date without any effective pharmacological management in clinic. Here, we tested whether nanoparticles based on polyethylenimine (PEI) and DNA could be a potential treatment. In mouse model of ALI induced by lipopolysaccharide (LPS) (10mg/kg), intravenous injection of PEI/DNA mediated a rapid (in 6h) and short-lived transgene expression in lung, with alveolar epithelial cells as major targets. When β2-Adrenergic Receptor (β2AR) was applied as therapeutic gene, PEI/β2AR treatment significantly attenuated the severity of ALI, including alveolar fluid clearance, lung water content, histopathology, bronchioalveolar lavage cellularity, protein concentration, and inflammatory cytokines in mice with pre-existing ALI. In high-dose LPS (40mg/kg)-induced ALI, post-injury treatment of PEI/β2AR significantly improved the 5-day survival of mice from 28% to 64%. These data suggest that PEI/DNA nanoparticles could be an effective agent in future clinical application for ALI treatment. From the Clinical EditorIn this novel study, PEI/DNA nanoparticles are presented as an effective agent for the treatment of the devastating and currently untreatable syndrome of acute lung injury, using a rodent model system.
Published Version
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