Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 9, Issue 8, Pages 1293-1303Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2013.05.004
Keywords
beta 2-Adrenergic receptor; Gene therapy; Lung epithelium; Nanoparticle; LPS-induced acute lung injury
Funding
- National Research Program for Biopharmaceuticals (NRPB) at NSC
- National Science Council (NSC) [100-2325-B-010-011, 100-2321-B-010-021]
- Aim for the Top University Plan of National Yang-Ming University [101ADP902]
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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 beta 2-Adrenergic Receptor (beta 2AR) was applied as therapeutic gene, PEI/beta 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/beta 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. (C) 2013 Elsevier Inc. All rights reserved.
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