Metal Polyphenol\nNanoparticle-Based Chemo/Ferroptosis\nSynergistic Therapy for the Treatment of Oral Squamous Cell Carcinoma

Despite the use of surgical resection and chemotherapy\nin the clinical\ntreatment of oral squamous cell carcinoma (OSCC), the 5-year survival\nrates of advanced patients are low. Therefore, more efficient strategies\nare urgently needed. Herein, a chemo/ferroptosis synergistic therapeutic\nsystem-DMEFe nanoparticles (NPs) is established for the treatment\nof OSCC. To create this system, the chemotherapeutic agent doxorubicin\n(DOX) was loaded into mesoporous silica nanoparticles and further\ncoated with a pH-sensitive metal polyphenol (iron ion and epigallocatechin\ngallate). These nanoparticles displayed excellent pH-sensitive drug-control\nrelease properties, and the release ratio of DOX at pH 5.5 was twice\nas high than that at pH 7.4. Additionally, DMEF NPs were effectively\ntaken up by the OSCC cell line SSC-25, which greatly impeded the proliferation\nof these cells. Notably, these nanoparticles increased the intracellular\nlevel of reactive oxygen species and effectively exhibited cytotoxity\neffects. The mechanistic results proved that DMEFe NPs regulated the\nexpression of ferroptosis-related genes to induce ferroptosis of SSC-25\ncells. Eventually, this chemo/ferroptosis therapeutic system exhibited\nremarkable antitumor effects and provided a novel strategy for the\ntreatment of OSCC.