TY - JOUR
T1 - Nanoparticle facilitated inhalational delivery of erythropoietin receptor cDNA protects against hyperoxic lung injury
AU - Ravikumar, Priya
AU - Menon, Jyothi U.
AU - Punnakitikashem, Primana
AU - Gyawali, Dipendra
AU - Togao, Osamu
AU - Takahashi, Masaya
AU - Zhang, Jianning
AU - Ye, Jianfeng
AU - Moe, Orson W.
AU - Nguyen, Kytai T.
AU - Hsia, Connie C W
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Our goals were to develop and establish nanoparticle (NP)-facilitated inhalational gene delivery, and to validate its biomedical application by testing the hypothesis that targeted upregulation of pulmonary erythropoietin receptor (EpoR) expression protects against lung injury. Poly-lactic-co-glycolic acid (PLGA) NPs encapsulating various tracers were characterized and nebulizated into rat lungs. Widespread NP uptake and distribution within alveolar cells were visualized by magnetic resonance imaging, and fluorescent and electron microscopy. Inhalation of nebulized NPs bearing EpoR cDNA upregulated pulmonary EpoR expression and downstream signal transduction (ERK1/2 and STAT5 phosphorylation) in rats for up to 21 days, and attenuated hyperoxia-induced damage in lung tissue based on apoptosis, oxidative damage of DNA, protein and lipid, tissue edema, and alveolar morphology compared to vector-treated control animals. These results establish the feasibility and therapeutic efficacy of NP-facilitated cDNA delivery to the lung, and demonstrate that targeted pulmonary EpoR upregulation mitigates acute oxidative lung damage.
AB - Our goals were to develop and establish nanoparticle (NP)-facilitated inhalational gene delivery, and to validate its biomedical application by testing the hypothesis that targeted upregulation of pulmonary erythropoietin receptor (EpoR) expression protects against lung injury. Poly-lactic-co-glycolic acid (PLGA) NPs encapsulating various tracers were characterized and nebulizated into rat lungs. Widespread NP uptake and distribution within alveolar cells were visualized by magnetic resonance imaging, and fluorescent and electron microscopy. Inhalation of nebulized NPs bearing EpoR cDNA upregulated pulmonary EpoR expression and downstream signal transduction (ERK1/2 and STAT5 phosphorylation) in rats for up to 21 days, and attenuated hyperoxia-induced damage in lung tissue based on apoptosis, oxidative damage of DNA, protein and lipid, tissue edema, and alveolar morphology compared to vector-treated control animals. These results establish the feasibility and therapeutic efficacy of NP-facilitated cDNA delivery to the lung, and demonstrate that targeted pulmonary EpoR upregulation mitigates acute oxidative lung damage.
KW - Aerosol nebulization
KW - Cytoprotection
KW - Gene therapy
KW - Hyperoxia
KW - Oxidative stress damage
KW - Poly-lactic-co-glycolic acid nanoparticles
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U2 - 10.1016/j.nano.2015.10.004
DO - 10.1016/j.nano.2015.10.004
M3 - Article
C2 - 26518603
AN - SCOPUS:84960116750
SN - 1549-9634
VL - 12
SP - 811
EP - 821
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 3
ER -