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

12 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

Fingerprint

Polyethyleneimine
Gene therapy
Acute Lung Injury
Genetic Therapy
Nanoparticles
DNA
Adrenergic Receptors
Lipopolysaccharides
Water content
Therapeutics
Genes
Alveolar Epithelial Cells
Lung
Proteins
Bronchoalveolar Lavage
Fluids
Transgenes
Intravenous Injections
Rodentia
Cytokines

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

Cite this

Polyethyleneimine and DNA nanoparticles-based gene therapy for acute lung injury. / Lin, Erh Hsuan; Chang, Hsiang Yi; Yeh, Shauh Der; Yang, Kuang Yao; Hu, Huei Sin; Wu, Cheng Wen.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 9, No. 8, 11.2013, p. 1293-1303.

Research output: Contribution to journalArticle

Lin, Erh Hsuan ; Chang, Hsiang Yi ; Yeh, Shauh Der ; Yang, Kuang Yao ; Hu, Huei Sin ; Wu, Cheng Wen. / Polyethyleneimine and DNA nanoparticles-based gene therapy for acute lung injury. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2013 ; Vol. 9, No. 8. pp. 1293-1303.
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