A new type of ultrasmall nanoprobes has recently been developed by our team for theranostic applications. These sub 5 nanometers nanoparticles are composed of a polysiloxane inorganic matrix and surrounded by chelates that can entrap gadolinium for MRI or radioactive isotopes for scintigraphy. The size of the particle leads to a complete renal elimination and no in vitro toxicity has been evidenced. The nanoparticles offer four different types of complementary imaging properties (MRI, Scintigraphy, Fluorescence Imaging, X-Ray tomography)[1]. They feature also an enhanced permeation and retention effect in tumours resulting in a concentration of the theranostic compound in the area of interest [2]. Coupling with peptides like cRGD has shown interesting preliminary results for increasing the concentration of the nanoparticles in the tumours by active targeting. The biodistribution of the nanoparticles after intravenous injection on gliosarcoma bearing rats (9L) revealed their retention in the tumour, together with their fast elimination from the surrounding healthy tissues. Considering the biodistribution results and the high in vitro radiosensitizing potential of the gadolinium based nanoparticles[3], a radiotherapy protocol has been implemented with an activation of the nanoparticles by the X-ray beam. The activation is fitted to occur when the concentration in particles is sufficient in the tumour to induce an effect and sufficiently weak in the surrounding tissue to avoid unwanted damages. This technique has led to a considerable increase of the lifespan of the gliosarcoma bearing rats. These preclinical results are really encouraging for further use of these compounds on patients, with the possibility to tailor the treatment to each patient through imaging techniques.

[1]F. Lux, A. Mignot, P. Mowat, C. Louis, S. Dufort, C. Bernhard, F. Denat, F. Boschetti, C. Brunet, R. Antoine, P. Dugourd, S. Laurent, L. Vander Elst, R. Muller, L. Sancey, V. Josserand, J.-L. Coll, V. Stupar, E. Barbier, C. Rémy, A. Broisat, C. Ghezzi, G. Le Duc, S. Roux, P. Perriat, O. Tillement, Angew. Chem. Int. Ed 123, 12507 (2011).

[2] G.Le Duc, I. Miladi, C. Alric, P. Mowat, E. Bräuer-Krisch, A. Bouchet, E. Khalil, C. Billotey, M. Janier, F. Lux, P. Perriat, S. Roux, O. Tillement, ACS Nano 5, 9566 (2011).

[3] P. Mowat, A. Mignot, W. Rima, F. Lux, O. Tillement, C. Roulin, M. Dutreix, D. Bechet, S. Huger, L. Humbert, M. Barberi-Heyob, M.-T. Aloy, E. Armandy, C. Rodriguez-Lafrasse, G. Le Duc, S. Roux, P. Perriat, Journal of Nanoscience and Nanotechnology 11, 7833 (2011)