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

To test the hypothesis that targeted upregulation of pulmonary erythropoietin (Epo) signaling via its receptor (EpoR) protects against lung injury, we encapsulated EpoR cDNA within poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs), and optimized nebulization into rat lungs. We observed sustained increases in EpoR protein expression and activation of downstream signal transduction - phospho/total ERK1/2 (shown) and STAT5 - peaking at 10 days and persisting up to 21 days, associated with attenuation of hyperoxia-induced lung injury. These results establish the feasibility and efficacy of a novel non-invasive approach of nanoparticle-facilitated gene therapy for acute lung injury.283