Abstract
Radiotherapy is a mainstay adjunctive therapy for glioblastoma (GBM). Despite the outcome improvement achieved with radiation, GBM prognosis remains dismal. Here we introduce a tumor-targeted iron oxide nanoparticle (NP) that intensifies the energy transfer of conventional photon radiotherapy on a selective cellular basis. Several NPs were formulated with systematic architectural variation to study and optimize reactive oxygen species (ROS) production. Selected from this screening stage, a biocompatible tumor-targeted NP was tested in vitro using two models of GBM, and then in vivo, using an orthotopic human primary GBM xenograft mouse model. Animals that received intravenous NP before irradiation demonstrated a 3-fold reduction in tumor growth and a 2-fold increase in survival. Cellular damage was investigated using in vivo magnetic resonance spectroscopy, which demonstrated increased therapeutic cytotoxicity specific to the tumor mass. Our work presents a viable therapeutic strategy to improve radiation therapy for GBM.
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