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

Erh Hsuan Lin, Hsiang Yi Chang, Shauh Der Yeh, Kuang Yao Yang, Huei Sin Hu, Cheng Wen Wu

Research output: Contribution to journalArticle

13 Citations (Scopus)

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) (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 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.

Original languageEnglish
Pages (from-to)1293-1303
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume9
Issue number8
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

Keywords

  • β2-Adrenergic receptor
  • Gene therapy
  • LPS-induced acute lung injury
  • Lung epithelium
  • Nanoparticle

ASJC Scopus subject areas

  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Medicine (miscellaneous)
  • Pharmaceutical Science

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