کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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877454 | 911026 | 2013 | 11 صفحه PDF | دانلود رایگان |

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) (10 mg/kg), intravenous injection of PEI/DNA mediated a rapid (in 6 h) 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 (40 mg/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.
Gene therapy could be a promising approach for treatments of a variety of chronic and acute diseases. However, it has not been sufficiently applied in ALI. The vector can be a major obstacle because both viral and non-viral vectors have serious drawbacks that limit their efficacies. In this study, we showed that nanoparticles formed by PEI/DNA can deliver genes in mouse lung even in the presence of pre-existing ALI. The gene delivery is rapid, efficient, and short-lived, with alveolar epithelial cells as major targets. These properties potentiate PEI/DNA nanoparticle to be an effective therapeutic agent in the treatment of ALI.Figure optionsDownload high-quality image (127 K)Download as PowerPoint slide
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 9, Issue 8, November 2013, Pages 1293–1303