Transferrin-Based Bismuth Nanoparticles for Radiotherapy with Immunomodulation Against Orthotopic Glioma

Modern radiotherapy frequently employs radiosensitizers for radiation dose deposition and triggers an immunomodulatory effect to enhance tumor destruction. However, developing glioma-targeted sensitizers remains challenging due to the blood-brain barrier (BBB) and multicomponent instability. This study aims to green-synthesize transferrin-bismuth nanoparticles (TBNPs) as biosafe radiosensitizers to enhance X-ray absorption by tumors and stimulate the immune response for glioma therapy. The proposed protein-based strategy provides TBNPs with BBB-crossing ability and prevents off-target toxicity. Cellular experiments following 4 Gy of X-ray irradiation reveal that TBNPs increase DNA damage in glioma cells and trigger immunomodulation, thereby inducing immunogenic cell death. Furthermore, TBNPs effectively inhibit tumor growth through synergistic radiotherapy and immunotherapy in an orthotopic glioma mouse model. The findings highlight TBNPs as promising radiosensitizers for effective and biosafe radiotherapy with immunomodulation.