Metal Polyphenol Nanoparticle-Based Chemo/Ferroptosis Synergistic Therapy for the Treatment of Oral Squamous Cell Carcinoma.

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