Nanoparticle facilitated inhalational delivery of erythropoietin receptor cDNA protects against hyperoxic lung injury

作者：Ravikumar Priya; Menon Jyothi U; Punnakitikashem Primana; Gyawali Dipendra; Togao Osamu; Takahashi Masaya; Zhang Jianning; Ye Jianfeng; Moe Orson W; Nguyen Kytai T^*; Hsia Connie C W^*

来源：Nanomedicine: Nanotechnology, Biology and Medicine , 2016, 12(3): 811-821.

DOI：10.1016/j.nano.2015.10.004

• Poly-lactic-co-glycolic acid nanoparticles
• Aerosol nebulization
• Oxidative stress damage
• Gene therapy
• Cytoprotection
• Hyperoxia

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.

• 出版日期2016-4