Project: NANOPARTICLES TO OPTIMIZE THE EFFECTS OF RADIOTHERAPY OF BRAIN TUMORS: MULTI-SCALE MODELING AND EXPERIMENTAL VALIDATION
| Acronym | RXNanoBRAIN (Reference Number: EURONANOMED2020-122) |
| Duration | 01/03/2021 - 01/03/2024 |
| Project Topic | Glioblastoma multiforme (GBM) is the most difficult brain cancer to treat. Major challenges are the limitation of irreversible brain damage and the infiltrative part of the tumor tissue which is the ultimate cause of recurrence. The therapeutic ratio can be widely improved using an image-guided radiation therapy (IGRT). Radiosensitization by metal-based nanoparticles (NPs) attracts significant interests and beyond this, radiotherapy is entering a new era with the emergence of promising clinical concepts for IGRT. We will design a novel theranostic AGuIX® design NP made of polysiloxane network, gadolinium (Gd) and bismuth (Bi) chelates that enable dual-modality (magnetic resonance (MR) and computed tomography (CT)) tumor imaging and radiation-dose enhancement providing clinicians with more options for precise tumor localization while mitigating toxicity in surrounding healthy tissue. We will demonstrate in animal models that the Gd-Bi AGuIX®-based NPs are highly compatible with current CT-guided radiation therapy and emerging MR guided approaches. As the extracellular matrix (ECM) plays pivotal roles in the infiltrative characteristics of GBM, to characterize the enhancement of radiosensitization, we will evaluate the cell-ECM interactions. As glioma-associated macrophages (GAMs) can be influenced by tumor derived cytokines, suppressing adaptive immune responses, their involvement will be characterized. Neuropilin-1 (NRP-1) overexpressed by angiogenic endothelial cells, is also implicated in GAM polarization. Using AGuIX® design NP conjugated to KDKPPR peptide specific to NRP-1, we will characterize vascular & immunological impacts. Non-invasive imaging using positron emission tomography with CT, MR spectroscopy and electron paramagnetic resonance oximetry, will allow us a complete longitudinal therapeutic monitoring. By performing short- and long-term molecular monitoring of inflammatory cytokines, we will enhance insight into the mechanisms of the immune reactions. |
| Network | EuroNanoMed III |
| Call | Joint Transnational Call (2020) |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Université de Lorraine (UL) | Coordinator | France |
| 2 | Oslo University Hospital (OUH) | Partner | Norway |
| 3 | NH TherAguix | Partner | France |
| 4 | Jagiellonian University (JU) | Partner | Poland |
| 5 | WPD Pharmaceuticals | Partner | Poland |