Abstract

Oral squamous cell carcinoma (OSCC), the most common oral malignancy, requires innovative therapeutic strategies. We developed a magnetic nanoparticle carrying verbascoside (VB-Fe 3 O 4 ) to enhance the bioavailability and antitumor efficacy of VB, a bioactive compound from Rehmannia glutinosa. VB-Fe 3 O 4 demonstrated superior tumor-targeting capabilities, achieving higher drug accumulation compared with free VB. In the human OSCC cell line HSC-3, VB-Fe 3 O 4 markedly induced apoptosis, inhibited proliferation and invasion through IL-6/STAT3 pathway. Mechanistic studies screened out intercellular cell adhesion molecule 1 (ICAM1) as the primary target of VB, with VB-Fe 3 O 4 suppressing IL-6-induced STAT3 phosphorylation. VB-Fe 3 O 4 downregulated metastasis-related genes, such as vascular cell adhesion molecule 1, mucin 1, ezrin, and invasion factor matrix metalloproteinase-9, were markedly decreased by VB-Fe 3 O 4 . VB-Fe 3 O 4 showed greater tumor suppression in OSCC transplanted tumors and experimental metastasis tumors compared with free VB. This nanoplatform synergistically combines precision delivery and molecular targeting, offering a promising treatment for OSCC management.