Abstract
Glioblastoma multiforme (GBM) is one of the most lethal malignant brain tumors in the central nervous system. Patients face many challenges after surgery, including tumor recurrence, intracranial pressure increase due to cavitation, and limitations associated with immediate postoperative oral chemotherapy. Here an injected peptide gel with in situ immunostimulatory functions is developed to coordinate the regulation of glutamine metabolism and chemodynamic therapy for overcoming these 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, this 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 within glioblastoma multiforme cells and improves a conducive immune microenvironment. Based on the concept of metabolic reprogramming, this treatment strategy has great potential to significantly reduce GBM tumor recurrence and prolong median survival in murine models.
Overview
- The primary focus of the study is to develop an injectable peptide gel that combines in situ immunostimulatory functions with glutamine metabolism regulation and chemodynamic therapy to overcome postoperative challenges in glioblastoma multiforme patients.
- The methodology involves crafting injectable gel scaffolds with short peptide molecules, incorporating the glutaminase inhibitor CB-839, and copper peptide self-assembled particles (Cu-His NPs) with chemodynamic therapy (CDT) efficacy.
- The primary objective of the study is to develop a treatment strategy that reduces glioblastoma multiforme tumor recurrence and prolongs median survival in murine models, based on the concept of metabolic reprogramming.
Comparative Analysis & Findings
- The study shows that the injectable peptide gel system heightens the therapeutic prowess of copper peptide particles in chemodynamic therapy, escalates intracellular oxidative stress, and induces augmented immunogenic cell death within glioblastoma multiforme cells.
- The system ultimately creates a conducive immune microenvironment, which is essential for the treatment of glioblastoma multiforme.
- The findings indicate that this treatment strategy has great potential to significantly reduce glioblastoma multiforme tumor recurrence and prolong median survival in murine models.
Implications and Future Directions
- The study's findings have significant implications for the treatment of glioblastoma multiforme, particularly in overcoming postoperative challenges and improving patient outcomes.
- Future studies should explore the efficacy of this treatment strategy in human patients and optimize its formulation and delivery to maximize therapeutic effect.
- Novel approaches, such as combining this treatment with other immunotherapies or targeted therapies, could enhance its therapeutic potential and improve treatment outcomes for glioblastoma multiforme patients.