Specialized iNANO Lecture: Biomedical applications of nanoparticles: new nanoplatforms for theranostic

Professor Nadine Millot, Department Nanosciences, Research Team Nanoparticles for biomedical applications, Laboratoire Interdisciplinaire Carnot de Bourgogne, ICB UMR 6303 CNRS/Université de Bourgogne Franche-Comté, Dijon, France

Biomedical applications of nanoparticles: new nanoplatforms for theranostic

The concept of nanomaterials that can be designed and administered into the human body to improve health is of great interest. During the past years there has been an increasing amount of research on the uses of nanomaterials in diverse areas of biomedical research including biological sensing, labelling, imaging, cell separation and therapy. Two promising nanostructures developed in ICB laboratory will be presented: SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) and Titanate Nanotubes (TiONts).

The SPIONs presented in this talk for multimodal imaging (MRI/PET and MRI/optical imaging) are developed by taking advantage of (i) the originality of their simultaneous synthesis and colloidal stabilization in one step through a continuous hydrothermal synthesis device [1, 2] and (ii) the association of these nanoparticles with innovative chelating agents (NODAGA, MANOTA etc.) or innovative fluorophores like phthalocyanine derivatives for near-IR detection and photodynamic therapy [3]. The imaging agents are stable under physiological conditions and show no cytotoxicity. Yields of radiolabeling indicate an efficient chelation and subsequent spectroscopic studies address the imaging capabilities of each probe in the well characterized SPIONs. In vitro, in vivo and biodistribution results of the final NPs will be presented [4].

The first evaluation of titanate nanotubes (TiONts) as a potential carrier of therapeutic molecules will be presented. These nanotubes are currently elaborated as stable suspensions of nanocarriers by surface chemistry engineering [5], and we have shown that TiONts are capable to increase the ionizing effect of radiation therapy in the case of glioblastoma [6] and can also be used as novel transfection agents for cardiomyocytes [7]. Furthermore, TiONts biodistribution has already been evaluated by SPECT/CT in male Swiss nude mice [8].

Docetaxel-Au-TiONts nanohybrids appear as versatile nanocarriers with the objective to avoid or to limit the systemic toxicity of taxanes and to improve the selectivity of radiotherapy. Our strategy is based on the intraprostatic injection of the docetaxel-Au-TiONts nanohybrids in replacement of brachytherapy and also in combination with radiotherapy. This will be achieved by taking advantage of the TiONts morphology as well as their radiosensitization effect and by associating them with docetaxel molecules (DTX) also recognized for their potential to radiosensitization. We also associate TiONts with gold nanoparticles, grafted on their surfaces, the latter being recognized for their radiosensitizing effect. Biodistribution kinetics showed that more than 70% of nanohybrids were localized into the tumor 96 hours after injection. Mice receiving nanohybrid-RT (Radiation Therapy) exhibited a significant tumor growth delay compared to mice receiving free DTX-RT [8].

References
[1] Maurizi L, Bouyer F, Paris J, Demoisson F, Saviot L, Millot N. One step continuous hydrothermal synthesis of very fine stabilized superparamagnetic nanoparticles of magnetite. Chem. Commun. 2011; 47: 11706-11708
[2] Thomas G, Demoisson F, Chassagnon R, Popova E, Millot N. One-step continuous synthesis of functionalized magnetite nanoflowers. Nanotechnology 2016; 27: 135604-135619
[3] Boudon J, Paris J, Bernhard Y, Popova E, Decréau R, Millot N. Magneto-Optical Nanomaterial: towards a step-by-step SPIO-Phthalocyanine scaffold with a view to bimodal imaging. Chem. Commun. 2013; 49(67): 7394-7396
[4] Maurizi L, Papa AL, Dumont L, Bouyer F, Vandroux D, Walker P, Millot N. Influence of surface charge and polymer coating on internalization and biodistribution of PEG-modified iron oxide nanoparticles, J. Biomed. Nanotechnol. 2015; 11: 126-136
[5] Papa AL, Maurizi L, Vandroux D, Walker P, Millot N. Synthesis of titanate nanotubes directly decorated with USPIO in hydrothermal conditions: a new detectable nanocarrier. J. Phys. Chem. C 2011; 115(39): 19012-19017
[6] Mirjolet C, Papa AL, Créhange G, Raguin O, Truc G, Maingon P, Millot N. The radiosensitization effect of titanate nanotubes as a new tool in radiation therapy for glioblastoma: a proof-of-concept. Radioth. Oncol. 2013; 108, 136-142
[7] Papa AL, Dumont L, Vandroux D, Millot N. Titanate nanotubes: towards a novel and safer nanovector for cardiomyocytes. Nanotoxicology 2013; 7(6): 1131-1142
[8] Boudon J, Papa AL, Paris J, Millot N. Titanate Nanotubes as a Versatile Platform for Nanomedicine. Nanomedicine One Central Press, UK, 2014 ISBN 978-1-910086-00-1

Host: Associate professor Brigitte Städler, Interdisciplinary Nanoscience Center & Department of Microbiology and Genetics, Aarhus University