Quercetin-loaded exosomes prevent endometrial fibrosis by downregulating EGFR

Intrauterine adhesions (IUA) are a common gynecological disorder characterized by endometrial fibrosis, driven by inflammation and stromal cell-to-myofibroblast transdifferentiation. IUA present significant clinical challenges due to high recurrence rates and drug resistance. While surgical adhesiolysis combined with estrogen therapy is the first-line treatment, its efficacy is limited in severe cases and relapse is common. Traditional Chinese medicine (TCM) offers a promising alternative, though the specific active components and mechanisms remain undefined. Here, we identified quercetin as a potent anti-fibrotic agent using network pharmacology; however, its clinical application is hindered by poor water solubility and low bioavailability. To overcome these limitations, we developed a quercetin-loaded exosome delivery system (Que-Exo). Compared to free quercetin, Que-Exo exhibited significantly superior anti-fibrotic efficacy at equivalent concentrations. Mechanistic investigations revealed that this therapeutic effect is mediated by the downregulation of the epidermal growth factor receptor (EGFR), thereby inhibiting fibrosis progression. These findings delineate the molecular mechanism of quercetin in IUA treatment and present an effective strategy to overcome its pharmacokinetic barriers, underscoring the therapeutic potential of Que-Exo for preventing endometrial fibrosis.