Synergistic Cemof Nanoplatform For Oscc Radiosensitization And Immune Microenvironment Remodeling

To address the dual challenges of radiotherapy resistance and immunosuppressive microenvironments in oral squamous cell carcinoma (OSCC), this study developed a cerium-based metal-organic framework (CeMOF) nanoplatform integrating radiosensitization and immunomodulation for enhanced antitumor efficacy. CeMOF was constructed leveraging the reversible Ce³⁺/Ce⁴⁺ redox properties to amplify reactive oxygen species (ROS) via Fenton-like reactions and radiocatalytic effects. The TIM-3 checkpoint inhibitor was loaded onto CeMOF to block immunosuppression and activate the cGAS-STING pathway. Therapeutic outcomes were systematically evaluated in tumor-bearing mice and cellular experiments. CeMOF significantly increased intratumoral ROS levels, achieving potent radiosensitization. The checkpoint inhibitor effectively inhibited TIM-3 signaling, promoted dendritic cell maturation, and enhanced CD8⁺ T-cell infiltration. The combined regimen demonstrated superior tumor suppression and prolonged survival in mice compared to monotherapies. This study presents a synergistic strategy combining CeMOF-mediated radiosensitization and TIM-3 blockade to remodel immunosuppressive microenvironments via "ROS amplification–immune activation," offering a promising approach for OSCC and other solid tumors.