PhD thesis : Metal oxide nanoparticles with a view to medical imaging and therapy: targeting of pathologies thanks to biological molecules.

Thesis subject :

Metal oxide nanoparticles with a view to medical imaging and therapy: targeting of pathologies thanks to biological molecules.

PhD thesis supervisors:

Main supervisor: Dr. Julien BOUDON, Co-supervisor: Prof. Nadine MILLOT

email : julien.boudon@u-bourgogne.fr, nadine.millot@u-bourgogne.fr,

web site : https://icb.u-bourgogne.fr/en/bh2n-en/

Scientific context:

The PhD thesis will be realized within the Nanosciences’ department of laboratory ICB of the university of Burgundy (Dijon, France). The successful candidate will be part of the interdisciplinary team BH2N and will work on topics ranging from the development of nanoparticles to toxicity and biocompatibility assays, from the state of the art to specific tests using platforms. In vitro and in vivo experiments are realized in collaboration with biologists (G. Lizard, Bio-peroxIL, C. Mirjolet, Centre Georges-François Leclerc CGFL and A. Béduneau, PEPITE).

For several years, the host team has been synthesizing nanoparticles of metal oxides. Its know-how has led to the development of nanohybrids as biological nanocarriers and contrast agents. On the other hand, the team and the laboratory are very well equipped with characterization techniques and have also access to an imaging platform thanks to CGFL (A. Oudot, EquipEx IMAPPI).

The objective of this thesis is the improvement of the diagnosis of different pathologies and their treatment by new nanotechnologies.

Description of the scientific project:

The idea is to develop a common functionalization approach for three different types of nanoparticles by controlling the number of active molecules on the surface of the nanoparticles, to control the grafting and stabilization provided by the intermediate functionalization layers on the surface of inorganic cores. For several years, the host team has developed several types of nanoparticles and their surface modification for various applications and among them: titanate nanotubes with a view to anti-cancer treatment, iron oxide nanoparticles for magnetic imaging and cardiac pathologies and, the newest one, tantalum oxide nanoparticles dedicated to tomodensitometry and targeting applications, possibly combined to gold NPs (in collaboration with S. Roux, UTINAM). But the complexity of the grafting of biological molecules (proteins, antibodies, etc.) on these nanohybrids requires an optimization of the surface functionalizations, some of them being brought by customized molecules in collaboration with the institute of molecular chemistry (C. Goze, ICMuB).

Finally, in close collaboration with biologists, in vitro studies will be realized by cytotoxicity assays on various cell lines and in vivo tests on mice will be considered to monitor the biodistribution of these nanohybrids by medical imaging as well as the evaluation of their imaging and therapeutic potentials.

This PhD thesis and its applications will be an opportunity to strengthen the collaboration started with, on the one hand the team of Prof. S. Lucas (Narilis, Belgium) and, on the other hand, Prof. M. Yada (Saga university, Japan) invited researcher in our team in 2019.

References related to the subject:

1. In vitro interaction and biocompatibility of titanate nanotubes with microglial cells, S. Sruthi, A. Loiseau, J. Boudon, F. Sallem, L. Maurizi, P. V. Mohanan, G. Lizard, N. Millot, Toxicol. Appl. Pharmacol. 353, 74-86 (2018)

2. Innovative Magnetic Nanoparticles for PET/MRI Bimodal Imaging, G. Thomas, J. Boudon, L. Maurizi, M. Moreau, P. Walker, I. Severin, A. Oudot, C. Goze, S. Poty, J.-M. Vrigneaud, F. Demoisson, F. Denat, F. Brunotte, N. Millot, ACS Omega 4, 2637-2648 (2019)

3. TitanateNanotubesEngineeredwithGoldNanoparticlesandDocetaxeltoEnhanceRadiotherapyon Xenografted Prostate Tumors, A. Loiseau, J. Boudon, A. Oudot, M. Moreau, R. Boidot, R. Chassagnon, N. M. Saïd, S. Roux, C. Mirjolet, N. Millot, Cancers, 11, 1962 (2019)

4. Influence of surface charge and polymer coating on internalization and biodistribution of PEG- modified iron oxide nanoparticles, L. Maurizi, A.L. Papa, L. Dumont, F. Bouyer, D. Vandroux, P. Walker, N. Millot, J. Biomed. Nanotechnol. 11, 126–136 (2015)

5. In vivo protein corona on nanoparticles: does the control of all material parameters orient the biological behavior? N. Singh, C. Marets, J. Boudon, N. Millot, L. Saviot, L. Maurizi, Nanoscale Adv., 3, 1209-1229 (2021)