TMIC-85. THE MECHANISM OF COMBINED HYDROGEN-CHEMICAL THERAPY BASED ON ACTIVE MAGNESIUM MICROMOTORS FOR INHIBITING GLIOBLASTOMA RECURRENCE BY MODULATING TUMOR MICROENVIRONMENT

Abstract OBJECTIVE This study aims to develop an innovative therapeutic strategy to prevent postoperative recurrence of Glioblastoma (GBM), a condition with poor prognosis and high recurrence rates. The focus is on exploring the efficacy of synergistic hydrogen-chemical therapy in inhibiting GBM recurrence, especially by reducing surgery-induced inflammation and enhancing the sensitivity of GBM cells to chemotherapy. METHODS The study employed the fabrication of Mg-Motor-DOX using a biodegradable polylactic acid-glycolic acid copolymer (PLGA) and gelatin containing Doxorubicin (DOX). The reaction of Mg with water produces hydrogen (H2), which aids in scavenging reactive oxygen species (ROS) and inflammation, alongside the specific release of chemotherapy drugs at the tumor site. A thermosensitive hydrogel was developed for in situ delivery of Mg-Motor-DOX to the tumor residual cavity. Additionally, RNA sequencing was used to study the transcriptional changes in the GBM tumor microenvironment (TME) induced by this therapy. RESULTS The study presents initial evidence of the in vivo efficacy of synergistic hydrogen-chemical therapy against GBM. The Mg-Motor-DOX mediated therapy not only scavenged ROS and reduced inflammation but also specifically released chemotherapy drugs at the tumor site, enhancing their effectiveness. RNA-Seq technology elucidated the molecular mechanisms underlying the therapy’s efficacy, revealing significant transcriptional changes in the GBM TME. CONCLUSION Synergistic hydrogen-chemical therapy, facilitated by Mg-Motor-DOX, shows promising potential in preventing the postoperative recurrence of GBM. This innovative approach effectively combines anti-inflammatory benefits and enhanced chemosensitivity, offering new strategies for GBM treatment. The molecular insights provided by RNA-Seq technology contribute to a deeper understanding of tumor treatment mechanisms, paving the way for future clinical applications.