Immunostimulatory hydrogel with synergistic blockage of glutamine metabolism and chemodynamic therapy for postoperative management of glioblastoma

Abstract

Glioblastoma multiforme (GBM) stands as one of the most lethal malignant brain tumors affecting the central nervous system. Post-surgery, patients encounter daunting challenges like tumor recurrence, increased intracranial pressure due to cavitation, and constraints linked with immediate postoperative oral chemotherapy. Herein, we construct an injected peptide gel with in situ immunostimulatory functions to harmonize the regulation of glutamine metabolism and chemodynamic therapy in tackling the postoperative obstacles. The methodology entails crafting injectable gel scaffolds with short peptide molecules, incorporating the glutaminase inhibitor CB-839 and copper peptide self-assembled particles (Cu-His NPs) renowned for their chemodynamic therapy (CDT) efficacy. By fine-tuning glutamic acid production via metabolic pathways, our system not only heightens the therapeutic prowess of copper peptide particles in CDT but also escalates intracellular oxidative stress. This dual mechanism culminates in augmented immunogenic cell death (ICD) within glioblastoma multiforme cells and improves a conducive immune microenvironment. Anchored on the tenets of metabolic reprogramming, this treatment strategy showcases substantial promise in significantly curtailing GBM tumor recurrence, prolonging median survival in murine models.