The two main limitations contributing to the failure of conventional therapy of certain solid tumors, among which glioblastoma is a typical example, are: i) treatment resistance ascribed to cell adaptation to environmental cues and ii) sub-optimal delivery of active principles. A major de facto objective of glioblastoma treatment is the exclusive eradication of tumor cells infiltrated in the central nervous system (CNS).
For more than 12 years our team has developed innovative micro and nanovectorisation-based strategies focusing on loco-regional delivery of anti-cancer medications in the CNS with demonstrated significant therapeutic benefit in preclinical models.
To further determine significance in humans and to better understand how these systems behave at the micro-nano-biological interface we now propose to focus on two main loco-regional approaches.
The first approach focuses on the development of novel nanovectorized internal radiation therapy combined with in situ radiosensitization. The choice of radiopharmaceuticals combined with the mode of delivery and intra-tumoral containment or targeting will be specifically addressed. The approach takes into account our new original data focusing on the nanoparticular targeting of the microRNA machinery involved in radioresistance. Milestones of this approach include the automation of the radiopharmaceutical formulation methods as well as the evaluation of the dosimetry correlated with biological responses.
The second approach focuses on implanting biointeractive “deposits” capable of interfering with tumor cell behavior (in terms of migration, differentiation and sensitivity to elimination signals) within the tumors or their resection cavities (perioperative surgery). This strategy is largely based on our expertise in the development of innovative formulations for releasing bioactive molecules (e.g. proteins). The aim of this project is to target cells to be eliminated and to modify their environment in order to attract and confine them in a controlled area for their destruction.
We expect to overcome key technological barriers limiting tissue homing and cellular and subcellular targeting of biomimetic vectors. We propose novel strategies for the targeting and elimination of radioresistant cells. The proposed work aims at developing relevant and optimized minimally invasive micro-nanomedicine strategies for the treatment of gliomas, as well as other solid tumors, by employing original and novel fundamental and technological approaches.
Emmanuel GARCION, Research Supervisor 2 Inserm
Frank BOURY, Professor
Olivier COUTURIER, Professor – Hospital Practitioner
François HINDRE, Lecturer
Franck LACOEUILLE, Lecturer – Hospital Practitioner
Philippe MENEI, Professor – Hospital Practitioner
Claudia MONTERO-MENEI, Lecturer
Audrey ROUSSEAU, Professor – Hospital Practitioner
6 Engineer and Technicians
Sylvie AVRIL, Research Technician Inserm
Blandine BOISSELIER, Hospital Engineer University Hospital Center
Anne CLAVREUL, Hospital Engineer University Hospital Center
Laurence SINDJI, Engineer Assistant Inserm
Clément TETAUD, Research Technician Angers University
Morgane MASSARD, Technician Angers University
1 Communication Officer
Mineke FAURE-EON, Project Manager – NanoFar+ Angers University
3 Post-doctoral fellows
Nela BUCHTOVA (NanoFar+)
Claire LOUSSOUARN, Inca « MARENGO », Inserm
Jean-Michel LEMEE, University Hospital Center
12 PhD Students (Programme)
Aurélien CONTINI (NanoFar Europe)
Gaëlle CORNE (LIST)
Hélène GREGOIRE (LABEX IRON)
Muhammad HAJI MANSOR (MESR)
Ulung Khoe KUSUMO (NanoFar Europe)
Hélène LAJOUS (Region Pays de la Loire – Europe)
Mathie NAJBERG (Region Pays de la Loire – Europe)
Milad POURBAGHI (NanoFar Europe)
Melody RIAUD (BioRegate)
Assia RMAIDI (Region Pays de la Loire)
Shabnam SHAHZAD (NanoFar Europe)
Deniz UGUR (NanoFar Europe)
3 Master 2
Raphël DIMA (Sciences Ingénierie Management de la Santé, Angers)
Céline BOURE (NanoFar+)
1- Sehedic D, Cikankowitz A, Hindre F, Davodeau F, Garcion E. Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones. Trends Pharmacol Sci (2015)
2- Clavreul A, Guette C, Faguer R, Tetaud C, Boissard A, Lemaire L, Rousseau A, Avril T, Henry C, Coqueret O, Menei P. Glioblastoma-associated stromal cells (GASCs) from histologically normal surgical margins have a myofibroblast phenotype and angiogenic properties. J Pathol (2014)
3- Vanpouille-Box C, Lacoeuille F, Belloche C, Lepareur N, Lemaire L, LeJeune JJ, Benoit JP, Menei P, Couturier O, Garcion E *, Hindre F *. Tumor eradication in rat glioma and bypass of immunosuppressive barriers using internal radiation with (188)Re-lipid nanocapsules. Biomaterials 32 (2011)
4- Roger M, Clavreul A, Venier-Julienne MC, Passirani C, Sindji L, Schiller P, Montero-Menei C, Menei P. Mesenchymal stem cells as cellular vehicles for delivery of nanoparticles to brain tumors. Biomaterials 31 (2010)
5- Paillard A, Hindre F, Vignes-Colombeix C, Benoit JP, Garcion E. The importance of endolysosomal escape with lipid nanocapsules for drug subcellular bioavailability. Biomaterials 31 (2010)