TY - JOUR
T1 - Polyethyleneimine and DNA nanoparticles-based gene therapy for acute lung injury
AU - Lin, Erh Hsuan
AU - Chang, Hsiang Yi
AU - Yeh, Shauh Der
AU - Yang, Kuang Yao
AU - Hu, Huei Sin
AU - Wu Lee, Cheng-Wen
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - Gene therapy
KW - LPS-induced acute lung injury
KW - Lung epithelium
KW - Nanoparticle
KW - β2-Adrenergic receptor
UR - http://www.scopus.com/inward/record.url?scp=84886421129&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2013.05.004
DO - 10.1016/j.nano.2013.05.004
M3 - Article
C2 - 23727098
AN - SCOPUS:84886421129
SN - 1549-9634
VL - 9
SP - 1293
EP - 1303
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 8
ER -