Fe₃O₄@Bi₂S₃ Nanoparticles Mediated MRI-Guided Precision Radiosensitization for Orthotopic Glioblastoma via External Magnetism

Radioresistance in tumors and the excess damage in normal tissues during radiotherapy (RT) restrict the clinical application of glioblastoma RT. Image-guided radiosensitization is hopefully adopted to achieve precision RT. Nevertheless, the therapeutic effect of radiosensitizers in glioblastoma is unsatisfactory due to limitations of the blood-brain barrier and poor tumor targeting. Herein, Fe₃O₄@Bi₂S₃ nanoparticles coated with a glioblastoma cell membrane (denoted as FBM) have been designed to sensitize RT. FBM accumulates precisely within the tumors via external magnetism and homologous adhesion capability. Afterward, FBM releases high-<i>Z</i> atoms (Bismuth) in ionizing radiation and tumor micro acidic environments that interact with ionizing radiation to generate high densities of secondary radiation, which leads to enhanced radiation dose deposits. Simultaneously, FBM generates reactive oxygen species, accumulates lipid peroxidation and Fe²⁺, depletes glutathione, and downregulates glutathione peroxidase 4 to activate ferroptosis. Notably, the tumor growth inhibition rate of FBM-mediated RT via external magnetism increases to 75.49% in the orthotopic glioblastoma model. Besides, FBM with magnetic resonance imaging performance shows the potential application in tumor diagnosis and therapy surveillance, thereby reducing damage to adjacent normal tissues and realizing MRI-guided precision RT. Hence, the novel multifunctional nanoplatform offers the potential for image-guided radiosensitization induced by activating ferroptosis, thus presenting an efficient radiotherapeutic approach for glioblastoma.