Biocompatible magnetic microparticles elaboration for cancer cells destruction

Published : 24 April 2017

The CEA/INAC SPINTEC lab offers a thesis opportunity on the synthesis of magnetic particles aimed at biomedical applications for targeted cancer cells killing. The approach we are developing consists in inducing spontaneous death by mechanical vibration of the particles, resulting from an externally applied rotating magnetic field. The mechanism for the cells death remains to be determined, but may proceed via apoptosis when functionalized particles are attached to the cell membrane, or by necrosis when they are internalized by the cell

Identification of the anti-tumor effect associated with mechanical vibrations has been realized in 2010[1] and, since, there have been several studies on this topic in our lab, in particular on the synthesis of dedicated magnetic particles – using techniques borrowed from microelectronics[2] – and their functionalization. The likely applicability of these particles for cancer therapy have been demonstrated, using in vitro experiments, in a recently defended doctorate thesis in our research team. [3] However, the extension of in-going work to in vivo studies – for which larger amount of particles is needed – requires to develop new processes for their fabrication.S

The thesis project consists in the development of the ball milling synthesis-process for magnetite particles, a material chosen for its biocompatibility. The study will consists in 1) the optimization of the particles magnetic properties; 2) the development of a process for their surface functionalization to ensure, on one hand, the dispersion of particles when in solution and, on the other hand, the binding selectivity on targeted cancer cells membrane; 3) preliminary studies regarding toxicity and mechanical response under applied magnetic field; 4) in vitro testing to assess the ability of these new particles to induce cancer cells death; 5) participation in the first in vivo tests on glioblastoma tumors with these biocompatible particles.

This study will be conducted in collaboration with the INAC SyMMES department for the functionalization and in vitro experiments, and CLINATEC-Lab – also from CEA Grenoble – for in vivo experiments.

The expected initial training for the candidate is a multi-disciplinary degree in nanosciences and nanotechnologies covering both physics and biology.

[1] “Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction”, D.-H. Kim, E. A. Rozhkova, I. V. Ulasov, S. D. Bader, T. Rajh, M. S. Lesniak, and V. Novosad, Nat. Mater. 9, 165 (2010).

[2] “Self-polarization phenomenon and control of dispersion of synthetic antiferromagnetic nanoparticles for biological applications”, H. Joisten, T. Courcier, P. Balint, P. Sabon, J. Faure-Vincent, S. Auffret, and B. Dieny, Applied Physics Letters 97, 253112 (2010). “Comparison of dispersion and actuation properties of vortex and synthetic antiferromagnetic particles for biotechnological applications”, S. Leulmi, H. Joisten, T. Dietsch, C. Iss, M. Morcrette, S. Auffret, P. Sabon, et B. Dieny, Applied Physics Letters 103, 132412 (2013).

[3] “Destruction de cellules cancéreuses par vibrations magnéto-mécaniques de micro/nano particules magnétiques : Élaboration des particules par approche top-down, biofonctionnalisation et tests in vitro”, S. Leulmi, Thèse de Doctorat, Université Joseph-Fourier, Grenoble (2014). http://www.theses.fr/s94192.

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