Oral squamous cell carcinoma (OSCC) remains one of the most aggressive malignancies of the oral epithelium, with limited therapeutic options effectively targeting both tumor growth and metastasis. Plant-derived nanovesicles have emerged as natural, biocompatible nanomedicines with potential applications in cancer therapy. Here, we systematically screened nanovesicles from ten medicinal plants and identified Panax notoginseng-derived nanovesicles (PnNVs) as the most potent inhibitors of OSCC. PnNVs exhibited favorable safety profiles and intrinsic tumor-homing ability, selectively accumulating in orthotopic tongue tumors. In vivo, they markedly suppressed primary tumor growth and lymphatic metastasis. Mechanistically, PnNVs disrupted redox homeostasis by inhibiting the p38-MAPK/NRF2 signaling pathway, thereby inducing ferroptosis, autophagy, and PANoptosis. In addition, PnNVs impaired cancer cell migration by modulating chemokine-associated signaling pathways critical for tumor dissemination. Multi-omic analyses further revealed synergistic contributions of RNA cargos and metabolite components to their multi-target anticancer efficacy. Collectively, our findings establish PnNVs as a natural, multifunctional therapeutic candidate with dual anti-proliferative and anti-metastatic activity, providing a promising preclinical strategy for OSCC treatment.
Chen et al. (Fri,) studied this question.