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Biomedical applications and nanotoxicity of iron-oxyde based nanohybrids

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Hyperthermia therapy is a medical treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anti-cancer drugs. Indeed, heating a living tissue at a temperature between 42°C to 46°C causes cell inactivation. The spectacular development of nanotechnology makes possible the use of heat sources at the nanoscale, activated by an external field. These nanosources provide decisive advantages compared to macroscopic implants. Among the different nanostructures proposed to mediate thermal ablation of cancerous cells, the use of magnetic nanoparticles is a very promising route. Indeed, the temperature increase required for hyperthermia can be achieved by using magnetic nanoparticles, which can be heated by the action of an external alternating magnetic field, because of the loss process that occurs during the reorientation of their magnetization.
This project is focused on the development and the optimization of iron oxide nanostructures dedicated for magnetic hyperthermia. The goal of this project is to work on two relevant questions regarding the use of nanometric heat generators for therapeutic hyperthermia :

(i) How can we maximize the heating capacity of the nanosources ? Magnetic hyperthermia depends on the size, shape, composition, atomic structure and local environment of the nanoparticles. It is therefore essential to understand the fine relation between these parameters and the heating properties of the nanosources. The atomic-scale characterization of the nanoparticles performed by using the outstanding performances of aberration–corrected electron microscopy, combined with magnetic measurements, provide concrete explanations of the nanosource heating performances. These indispensable information give us an unprecedented opportunity to synthesize optimized nanosources by using the flexibility of the present chemical fabrication methods.

NPs used in this project. (a) Highly monodispersed nanoparticles, (b) Nanocubes, (c) high resolution image of a nanoflower (power spectrum in insert)

(ii) The therapeutic use of nanomaterials raises also the questions of the biodistribution and biodegradation of the nano-agents inserted into the patient body. Therefore, we have studied the long-term aging of the nanosources in the cellular medium. We use magnetic measurements adapted to characterization of nanoparticles in biological environment (ferromagnetic resonance, SQUID) and the multi-functionalities of transmission electron microscopy to highlight the structural and magnetic transformations due to the nanoparticles / cells interactions.
This original multi-scale approach is now exploited to provides precious information on the life cycle and related toxicity of many nanomaterials in the organism, which are of high interest for a very broad scientist audience.

Lisosome extracted from the liver of a mouse, 24 hours after the injection of iron oxide NPs. (a) STEM image (b) Fe map obtained by EDX. (c) Electron diffraction confirming the face centred cubic structure (space group Fd3m) of the injected NPs.

Collaborators :

CNRS Defi Nano project : NanoMetroBio

- Florence Gazeau and Claire Wilhelm, MSC laboratory (Univ. Paris 7)
- Rana Bazzi, LI2C (Univ. Paris 6)
- Teresa Pelligrino (National Nanotechnology Laboratory of CNR-NANO, Italy)

Publications :

Carbon Nanotube Degradation in Macrophages : Live Nanoscale Monitoring and Understanding of Biological Pathway
Dan Elgrabli, Walid Dachraoui, Cécilia Ménard-Moyon, Xiao Jie Liu, Dominique Bégin, Sylvie Bégin-Colin, Alberto Bianco, Florence Gazeau, and Damien Alloyeau
ACS Nano, DOI : 10.1021/acsnano.5b03708

Anthropogenic Carbon Nanotubes Found in the Airways of Parisian Children
Jelena Kolosnjaj-Tabi, Jocelyne Just, Keith B. Hartman, Yacine Laoudi, Sabah Boudjemaa, Damien Alloyeau, Henri Szwarc, Lon J. Wilson, Fathi Moussa
Ebiomedicine, doi:10.1016/j.ebiom.2015.10.012

The One Year Fate of Iron Oxide Coated Gold Nanoparticles in Mice
Jelena Kolosnjaj-Tabi, Yasir Javed, Lénaic Lartigue, Jeanne Volatron, Dan Elgrabli, Iris Marangon, Giammarino Pugliese, Benoit Caron, Albert Figuerola, Nathalie Luciani, Teresa Pellegrino, Damien Alloyeau, and Florence Gazeau
ACS Nano, 9, 7925

Biodegradation Mechanisms of Iron Oxide Monocrystalline Nanoflowers and Tunable Shield Effect of Gold Coating
Yasir Javed, Lénaic Lartigue, Pierre Hugounenq, Quoc Lam Vuong, Yves Gossuin, Rana Bazzi, Claire Wilhelm, Christian Ricolleau, Florence Gazeau, Damien Alloyeau

Life cycle of magnetic nanoparticles in the organism
J Kolosnjaj-Tabi, Y Javed, L Lartigue, C Péchoux, N Luciani, D Alloyeau, F Gazeau
Biologie aujourd’hui 208 (2), 177-190

Biodegradation of iron oxide nanocubes : high-resolution in situ monitoring
Lénaic Lartigue, Damien Alloyeau, Jelena Kolosnjaj-Tabi, Yasir Javed, Pablo Guardia, Andreas Riedinger, Christine Pe´choux, Teresa Pellegrino, Claire Wilhelm, Florence Gazeau
ACS nano 7 (5), 3939-3952

Cooperative Organization in Iron Oxide Multi-Core Nanoparticles Potentiates their Efficiency as Heating Mediators and MRI Contrast Agents
Lenaic Lartigue, Pierre Hugounenq, Damien Alloyeau, Sarah P Clarke, Michael Levy, Jean-Claude Bacri, Rana Bazzi, Dermot F Brougham, Claire Wilhelm, Florence Gazeau
ACS Nano 6, 10935

Iron Oxide Monocrystalline Nanoflowers for Highly Efficient Magnetic Hyperthermia
P. Hugounenq, M. Levy, D. Alloyeau, L. Lartigue, E. Dubois, V. Cabuil, C. Ricolleau, S. Roux, C. Wilhelm, F. Gazeau, and R. Bazzi
Journal of Physical Chemistry C, 116, 15702

Long term biotransformation of iron oxide nanoparticles in the organism
Michael Levy, Nathalie Luciani, Damien Alloyeau, Dan Elgrabli, Vanessa Deveaux, Christine Pechoux, Sophie Chat, Guillaume Wang, Nidhi Vats, François Gendron, Cécile Factor, Sophie Lotersztajn, Alain Luciani, Claire Wilhelm, Florence Gazeau
Biomaterials, 32, 3988 (2011)

Correlating Magneto-Structural Properties to Hyperthermia Performance of Highly Monodisperse Iron Oxide Nanoparticles Prepared by a Seeded-Growth Route
Michael Levy, Alessandra Quarta, Ana Espinosa, Albert Figuerola, Claire Wilhelm, Mar García-Hernández, Alessandro Genovese, Andrea Falqui, Damien Alloyeau, Raffaella Buonsanti, Pantaleo Davide Cozzoli, Miguel Angel García, Florence Gazeau and Teresa Pellegrino
Chemistry of Materials, 23, 4170–4180