Glioblastoma multiforme (GBM) remains one of the most lethal brain tumors, characterized by metabolic plasticity, redox adaptability, immunosuppressive microenvironment, and limited treatment penetration of the blood-brain barrier (BBB). This article introduces a multifunctional Cu3PdN@CR nanoplatform, combining metabolic disruption and sonodynamic activation to enhance iron exudation and copper phosphatization, while also enhancing immunotherapy. The phase transition from selenocopper 3N to doped germanium 3N semiconductors transforms the material from a semiconductor to a semi-metal with a narrowed band gap, enhancing redox activity for glutathione (GSH) depletion and reactive oxygen species (ROS) generation, thereby inducing oxidative imbalance and mitochondrial collapse. Combined with cholesterol oxidase (COD), it further reduces cholesterol and downregulates PD-L1, triggering metabolic stress and immune remodeling. The RVG29 peptide promotes BBB penetration and glioma targeting, while ultrasound (ultrasound) stimulation enhances ROS production. This cascade reaction triggers immunogenic cell death (ICD), evidenced by calreticulin exposure and ATP release, thereby promoting the maturation of dendritic cells and CD8+ T cell infiltration. In the orthotopic GBM model, Cu3PdN@CR significantly inhibits tumor growth, prolongs survival, and has no systemic toxicity. Overall, this study establishes a BBB-permeable, enhanced nanoplatform as a promising iron exudation/copper chelation therapy strategy for effective GBM treatment. This study was published in ACS Nano under the title "Enhanced Immunotherapy for Glioblastoma Using a Cholesterol Oxidase-Loaded, Pd-Doped Cu3N Nanozyme-Based Multimodal Nanoplatform".
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DOI: 10.1021/acsnano.6c00714