Development of immuno-radiosensitizing nanoparticles for glioblastoma

Anasthasia Ilongo-Koumba – PhD Student, Université de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 CAEN, France; Abdallah Amedlous – PhD, Université de Caen Normandie, ENSICAEN, CNRS, LCS, Laboratoire Catalyse et Spectrochimie, 14000 Caen, France; Fabien Fillesoye – assistant engineer, Université de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 CAEN, France; Valérie Ruaux – Ingineer, Université de Caen Normandie, ENSICAEN, CNRS, LCS, Laboratoire Catalyse et Spectrochimie, 14000 Caen, France; Marie Lozier-Desmurs – assistant engineer, Université de Caen Normandie, ENSICAEN, CNRS, LCS, Laboratoire Catalyse et Spectrochimie, 14000 Caen, France; Svetlana Mintova – Head of Research, Université de Caen Normandie, ENSICAEN, CNRS, LCS, Laboratoire Catalyse et Spectrochimie, 14000 Caen, France; Samuel Valable – Head of Research, Université de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 CAEN, France; Clément Anfray – PhD, Université de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 CAEN, France

Introduction:

Treatments for glioblastoma (GBM) are not sufficiently effective. Its resistance to radiotherapy (RT) stems from intrinsic factors and severe tumor hypoxia, as RT efficacy depends on oxygen levels¹. GBM is a "cold" tumor microenvironment, infiltrated by pro-tumoral tumor-associated macrophages (TAMs). Strategies are explored to overcome these challenges: radiosensitizing the tumor with gadolinium (Gd)², reoxygenating it by in situ H₂O₂ decomposition, catalyzed by manganese (Mn)³ and reprogramming TAMs to an anti-tumoral phenotype using TLR agonists like resiquimod (R848)⁴. The aim is to combine these strategies to develop a multimodal therapeutic nanoparticle (MTNP).