Fig. 1: Schematic overview.
mnbTSLP-iLNPBUD5 self-assembles through microfluidics and is aerosolized with a vibrating mesh nebulizer for pulmonary delivery. After internalization via membrane fusion and GR-mediated endocytosis, mnbTSLP-iLNPBUD5 escapes from lysosomes, releasing its cargo, mnbTSLP and budesonide, into the cytoplasm. The therapeutic mnbTSLP subsequently translates into nbTSLP, which is secreted extracellularly to neutralize overexpressed TSLP in the asthmatic airway environment, preventing the phosphorylation of STAT3 and p38 and restoring budesonide sensitivity. Consequently, the GR complex formed by budesonide’s interaction with GR successfully translocates to the nucleus, modulating the transcription of inflammatory genes. Taken together, the synergistic combination of budesonide and nbTSLP alleviates asthma symptoms, including inflammatory cell infiltration, pro-inflammatory cytokine production, goblet cell hyperplasia, and smooth muscle hypertrophy, leading to the regression of asthma and the restoration of a healthy airway.
