期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 12, 期 3, 页码 811-821出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2015.10.004
关键词
Poly-lactic-co-glycolic acid nanoparticles; Aerosol nebulization; Oxidative stress damage; Gene therapy; Cytoprotection; Hyperoxia
资金
- National Heart, Lung and Blood Institute [R01 HL40070, U01 HL111146, HL110967]
- National Institute of Diabetes, Digestive and Kidney Diseases [R01-DK091392, DK092461]
- Charles and Jane Pak Foundation
- O'Brien Kidney Research Center [P30-DK-07938]
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. (C) 2015 Elsevier Inc. All rights reserved.
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