BBB-Penetrative Metformin-MnO2 Hybrid Nanoparticles for Enhancing Radiotherapy of Glioblastoma Multiforme
Azhar Abbasi – Research Associate, University of Toronto; Chungsheng He – Research Associate, University of Toronto; Jeffrey Henderson – Professor, University of Toronto; Michael Milosevic – Professor, University of Toronto; Liting Wang – Post Doctoral Fellow, Univeristy of Toronto; Xiao Yu Wu – Professor, University of Toronto
Ph.D Candidate University of Toronto Toronto, Ontario, Canada
Introduction:
Radiotherapy, a main treatment for aggressive and inoperable glioblastoma multiforme (GBM), is hindered by hypoxia and immunosuppressive tumour microenvironment (TME). Despite attempts to deliver radiosensitizers, their penetration to the GBM is limited by the blood-brain barrier (BBB) and abnormal vasculature, necessitating higher radiation doses that damage healthy brain tissues. To address this, we have developed bioactivatable BBB-penetrative metformin-MnO₂ polymer-lipid nanoparticles (TP-MetMDNPs) to synergistically increase O2 abundance in TME, activate cGAS-STING pathway, reduce PD-L1 and VEGF, and enhance immunogenic cell death (ICD) and anti-tumour immunity (Fig.1).
Learning Objectives:
Understand the different ways TP-MDNP and Metformin can modulate the tumour microenvironment synergistically.
Describe how TP-MetMDNPs can be used as theranostic agents.
Explain the therapeutic benefits of adjuvant administration of TP-MetMDNP with radiotherapy.
