GRAFTED METAL OXIDE NANOPARTICLES AS A TOOL FOR CELLULAR IMAGING: FROM IN SILICO TO IN VIVO APPLICATIONS

Dr. DELVILLE Marie-Hélène

Institut de Chimie de la Matière Condensée de Bordeaux, UPR 9048 – CNRS, Université Bordeaux

87 Avenue du Dr. A. Schweitzer, 33608 Pessac cedex, France

e-mail: delville@icmcb-bordeaux.cnrs.fr

 

Nanoparticles and their control are of great interest from both academic and industrial points of view, with numerous applications in domains such as medicine, catalysis and material sciences. This talk will stress on metal oxide nanoparticles (NPs) and two main aspects: their use as multifunctionnalcontrast agents1 and their potential nanotoxicity2.

As multifunctionnalcontrast agents, they can provide a multiple targeting and vizualisation of organs or cells with both detectable changes in the MR signal intensity of the target tissue or organ by changing its MR relaxation properties and classical detectable optical signals for example.3,4, In a second step, we focused on the development of biocompatible nanoparticles with an external shell of high-spin paramagnetic lanthanide contrast agents like gadolinium chelate (seven unpaired electrons), and europium fluorescent probes for targeted imaging.5,6

We will also present preliminary results on the introduction of a superparamagnetic oxide in the silica and study the interactions in between the shell and the core with respect to the silica shell thickness.7

A second aspect of the NPS world is their nanotoxicology which has also attracted the attention of public and governments’ worldwide. The established methods of chemical safety assessments have to be modified to address the special characteristics of nanoparticles and more especially to assess the biological effects of these highly reactive materials.

There is an urgent need to evaluate the risks of these particles to ensure their safe production, handling, use, and disposal. In particular, the behavior of nanoparticles inside living cells is still an enigma, and no metabolic responses induced by these particles are understood so far.

With this respect, we have examined the potential toxicity due to exposure of TiO2 NPs used in sunscreens and cosmetics. We applied an original imaging methodology (Ion Beam Analysis, TEM, & Confocal microscopy) to in vitro and in vivo studies, combining technologies for the detection, tracking, and quantification of TiO2 nanoparticles as well as the use of indicators for ion homeostasis, cell metabolism, or cell fate. Our main goal is to precisely identify the molecular and cellular mechanisms involved in the nanotoxicity of TiO2 nanoparticles in eukaryotic cells and in multi-cellular organisms such as Caenorhabditis elegans (C. elegans) .

1 Emeline Julie Ribot, Sylvain Miraux, Marie-Hélène Delville, Sabrina Lacomme, Etienne Gontier, Anne-Karine Bouzier-Sore, Véronique Bouchaud, Jean-Michel Franconi, Eric Thiaudiere, Pierre Voisin Contrast Media and Molecular Imaging 2009, 4 (3), 109-117

2 Marina Simon, Philippe Barberet, Marie-Hélène Delville, Philippe Moretto, Hervé Seznec Nanotoxicology, 2011, 5 (2), 125-139.

3 P. Voisin, E.J. Ribot, S. Miraux, A.K. Bouzier-Sore, J.F. Lahitte, V. Bouchaud. S. Mornet, E. Thiaudière, J.-M. Franconi, L. Raison, C.Labrugre, M.H. Delville Bioconjugate Chem. 2007,18, 1053-1063.

4 Ribot EJ, Miraux S, Konsman JP, Bouchaud V, Pourtau L., Delville MH, Franconi JM, Thiaudière E, Voisin PJNMR Biomed. 2011 Article first published online: 8 MAR 2011 | DOI: 10.1002/nbm.1699 .

5 Ribot, E.; Bouzier-Sore, A.-K.; Bouchaud, V.; Miraux, S.; Delville, M.-H.; Franconi, J.-M.; Voisin, P. Cancer Gene Therapy 2007, 14,724-737.

6 S.L.C. Pinho, H. Faneca, C.F.G.C. Geraldes, M.H. Delville, L.D. Carlos, J.Rocha, Biomaterials, in press.

7 Sonia L. C. Pinho, Giovannia A. Pereira, Pierre Voisin, Jinane Kassem, Véronique Bouchaud, Laetitia Etienne Joop A. Peters, Luis Carlos, Stéphane Mornet, Carlos F.G.C. Geraldes, João Rocha, Marie-Hélène Delville. ACS Nano, 2010, 4, 5339-5349.