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Molecular Imaging and Delivery of Active Substances

MEFISTO project


Targeted biological nano-magnets for theranostic

Published on 28 November 2017

4 years duration, ANR grant AAP P2N 2012, coordinator D. Pignol (LBC)

 

The MEFISTO project aims to obtain the proof of concept that functionalized biological nano‑magnets (called magnetosomes) can be used for the localized treatment by hyperthermia of cerebral tumors, assisted by high‑field Magnetic Resonance Imaging (MRI) diagnosis. These nanoparticles, which are produced by magnetotactic bacteria, regroup five characteristics of interest for biomedical applications that define a new type of theranostic agent: i) a perfectly crystalline and regular nanocrystal of magnetite, with contrasting properties for MRI; ii) magnetic properties that allow easy separation or guidance; iii) a natural lipid bilayer coating the iron oxide crystal, ensuring its solubilization; iv) a possible functionalization of the lipid surface with biological functions for cellular targeting or in situ enzymatic catalysis; v) a therapeutic action due to the ferric composition, that can generate a localized hyperthermia under focused radiofrequency excitation.

During the course of this 4 years project, magnetosomes will be genetically functionalized with relevant peptides or proteins, which are able to interact with one specific biological target of medical interest (biomarkers of neoangiogenesis in a rodent model of human glioblastoma). The MRI contrasting properties of these functionalized magnetic nanoparticles will be characterized using high magnetic field scanner (11.7T). The expected enhancement of in vivo MRI sensitivity would allow a more precise localization of tumoral vessels with lower injected doses of contrast agent. The development of a localized treatment by cerebral hyperthermia, assisted by MRIbased diagnosis, will be entrusted to Nanobactérie, the industrial partner that develops thermotherapy strategies for cerebral tumors treatment with non-functionalized magnetosomes (world patent). In addition to the demonstration of this new theranostic concept that can be extended to other pathologies, we will record detailed physiological data on the chosen animal model (toxicity, biodistribution and immunogenicity), that are absolutely needed to decide further translation to clinical applications. The deliverable of MEFISTO project is a non-toxic and functionalized nanoobject, allowing high-field MRI diagnosis of cerebral tumors and their treatment by magnetic hyperthermia.

 
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