MAGNETIC NANO-THERAPIES :   MICROVESICLES, HYPERTHERMIA AND TISSUE ENGINEERING



Laboratoire Matière et Systèmes Complexes MSC, UMR7057, CNRS & University Paris Diderot.
Cell therapies and medically oriented nanotechnologies are currently among promising biotechnologies. One attractive approach is to associate magnetic nanoparticles with cells in order to supply them with sufficient magnetization to be detectable by MRI,  manipulated by magnetic forces, or treated with therapeutic hyperthermia.
Recently we examined the influence of the amount of internalized iron and the state of nanoparticle aggregation on the capacity for mesenchymal stem cell differentiation and MRI single cell tracking. We demonstrated that high resolution Magnetic Resonance Imaging (MRI) allowed combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth.
Inside the cells, the nanoparticles concentrate in pre-existing intracellular membrane-bound vesicles known as endosomes. This renders these compartments magnetic, and allows them to be manipulated within the intracellular environment by applying an external rotating magnetic field in order to explore the local mechanical properties of the cell interior.
Another promising field of applications concerns the development of tissue engineering mediated by cellular magnetic force to mimic the most closely multicellular organisations found in the living. The aim is to confine stem cells in three dimensions at the millimetric scale by using home-designed miniaturized magnetic devices, in order to create cellular patterns for stem cell differentiation and tissue engineering.
Magnetic nanoparticles can also be used as heat sources for magnetic hyperthermia. Under the influence of an alternating high frequency magnetic field, they generate heat through relaxation processes. Cellular internalisation of magnetic nanoparticles localises the source of heat in the internal volume of the cell, with direct application for tumour cell therapies.

Finally, we investigate the issue of the becoming of the nanoparticles after their internalization, and evidenced some release within microvesicles. These biogenic vesicles could be engineered to attain multiple responsiveness, and provide them with therapeutic and imaging functions.


PEOPLE
Claire Wilhelm, publications
Nathalie Luciani
Myriam Reffay
Ana Espinosa, postdoctorant
Kelly Aubertin, phD student
Vicard Du, phD student
François Mazuel, PhD student
PREVIOUS MEMBERS
Guillaume Frasca - phD defense on october 2010
Damien Robert - phD defense on december 2010
Delphine Fayol - phD defense on october 2012
Amanda Silva, postdoctorant 2010-2012
Riccardo Di Corato, postdoctorant 2011-2013


COLLABORATORS

MSC lab : Florence Gazeau, Amanda Silva Brun, Jean-Claude Bacri, Cyprien Gay

PHENIX, University Paris 6 : Christine Ménager, Sophie Neveu, Ali Abou-Hassan
IIT, Genova, Italy : Teresa Pellegrino
Biological Adaptation and Ageing. UMR 8256 CNRS, University Paris 6 : Onnik Agbulut
UMR 1148 - Laboratoire de recherche vasculaire translationnelle : Didier Letourneur
Laboratoire d'ingénierie ostéo-articulaire et dentaire, Nantes : Catherine Le Visage
PARCC, HEGP hospital : Olivier Clément, Laetitia Pidial, Gabriel Rahmi


FUNDINGS