Polyethyleneimine and DNA nanoparticles-based gene therapy for acute lung injury

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• 作者：Erh-Hsuan Lin ; Hsiang-Yi Chang ; Shauh-Der Yeh ; Kuang-Yao Yang ; Huei-Sin Hu ; Cheng-Wen Wu
• 关键词：尾2-Adrenergic receptor ; Gene therapy ; Lung epithelium ; Nanoparticle ; LPS-induced acute lung injury
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：November, 2013
• 年：2013
• 卷：9
• 期：8
• 页码：1293-1303
• 全文大小：2862 K

文摘

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 尾2-Adrenergic Receptor (尾2AR) was applied as therapeutic gene, PEI/尾2AR 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/尾2AR 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 Editor

In 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.