Although radiotherapy has been established as a major therapeutic modality for glioma, radical new avenues are critically needed to prevent inevitable tumor recurrence. Herein, we utilized a magnetic nanoparticle-based platform with cationic polymer modification to promote radiotherapy for glioma treatment. We found that the nanoplatform induced cytotoxicity to glioma cells under radiation as well as promoting significant survival benefits in both immunocompetent and aythmic mice with glioma. Utilizing the magnetic properties of the nanoparticles, we were able to ascertain that myeloid derived suppressor cells (MDSC) were taking up nanoparticles in the brain tumor. The observed efficacy was attributed to destruction of glioma cells as well as MDSCs repolarization from immunosuppressive phenotype to a pro-inflammatory phenotype, which promoted antitumor effects and synergistically promoted radio-therapeutic effects. Our nanoparticles provide a robust dual-targeting platform for glioma radiotherapy by simultaneous eradication of tumor cells and manipulation of myeloid phenotypes in the central nervous system.
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