Wogonin-Loaded PLGA Sustained-Release Nanomicelle Inhibiting EGFR Pathway for Antitumor Effects in OSCC

Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the head and neck. Current treatment strategies, including surgery, radiotherapy, and chemotherapy, are limited by moderate efficacy and severe side effects, highlighting the need for novel therapeutic approaches. Wogonin (Wo), a natural flavonoid, has shown antiproliferative, pro-apoptotic, and antimetastatic activities in various cancer models; however, its effect on OSCC has not been investigated. In this study, Wo-loaded poly(lactic-co-glycolic acid) nanoparticles (PW NPs) were prepared to enhance water solubility and achieve sustained drug release. In vitro assays, including CCK-8, flow cytometry, live/dead staining, and wound healing assays, revealed that PW NPs significantly inhibited OSCC cell proliferation, induced apoptosis, and reduced cell migration. Network pharmacology analysis and qRT-PCR further suggested that Wo exerts its therapeutic effects through the EGFR signaling pathway. Hemolysis testing and histological examination of major organs confirmed the favorable biocompatibility of the nanoparticles. This study provides the first systematic evidence of the therapeutic potential of Wo in OSCC and lays a foundation for its further preclinical development.