Extracellular vesicles targeting EGFR inhibit MAOA expression and activity by delivering curcumin for the treatment of asthma.

AIMS: To investigate whether curcumin (CUR) delivered by EGFR-targeted extracellular vesicles (EVs) alleviates asthma and to explore the underlying mechanism.

MATERIALS AND

METHODS

CUR was loaded into mouse bone marrow mesenchymal stem cell‑derived EVs. A bispecific fusion protein, ZEGFR‑CP05 (EGFR‑specific affibody linked to a CD63‑binding peptide), was used to modify EVs. Therapeutic efficacy and targeting were evaluated in an ovalbumin (OVA)‑induced acute asthma mouse model.

RESULTS

ZEGFR‑CP05‑EVs showed enhanced lung accumulation. In asthmatic mice, ZEGFR‑CP05‑EVs‑CUR reduced airway inflammation, goblet cell hyperplasia, collagen deposition, and EGFR expression. Network pharmacology combined with experimental validation identified monoamine oxidase A (MAOA) as a novel target. Treatment suppressed MAOA expression and activity, restored serotonin (5‑HT) levels, and decreased reactive oxygen species (ROS) generation.

CONCLUSIONS

ZEGFR‑CP05‑EVs mediated curcumin delivery alleviates asthma pathology by inhibiting MAOA, highlighting a promising therapeutic strategy.