Magnetic Nanoparticles as a Theranostic Platform in Brain Tumor Treatment: Surmounting the Bench-to-Bedside Barriers.

Malignant brain tumors, particularly glioblastoma, remain one of the greatest challenges in oncology due to their invasive nature, therapeutic resistance, and protection by the blood-brain barrier. Decades of limited therapeutic progress underscore the need for new treatment strategies beyond conventional modalities. Magnetic nanoparticles have emerged as a promising theranostic platform that integrates high-precision imaging, targeted delivery, and synergistic therapy. In this review, we outline a mechanistic framework for magnetic nanoparticle applications, with a focus on the link between ferroptosis and immune activation. We discuss how the intrinsic properties of magnetic nanoparticles can be engineered to induce iron-dependent ferroptotic cell death, which may help overcome apoptosis resistance and also trigger immunogenic cell death. This magnetic nanoparticle-induced immunogenic cell death may shift the immunosuppressive brain tumor microenvironment from a "cold" state toward a more immune-active phenotype, thereby supporting combination immunotherapy. We also examine key translational challenges and potential solutions, including quantitative magnetic particle imaging-guided therapeutic dosimetry, focused ultrasound-mediated delivery strategies, and issues related to Chemistry, Manufacturing, and Controls and regulatory science. By analyzing these translational challenges, this review aims to highlight practical considerations for advancing magnetic nanoparticle-based therapies toward clinical neuro-oncology.