Targeted biological nano-magnets for theranostic – MEFISTO

The MEFISTO project is set in an experimental development framework where scientific, technical and technological knowledge of our consortium are coordinated to realize the proof of concept and the development required for the utilization of functionalized biological nano-magnets (the magnetosomes) in the localized treatment by hyperthermia of cerebral tumors assisted by high-field Magnetic Resonance Imaging (MRI) diagnostics. These nano-particles, 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 allows easy separation or guidance ; (iii) a natural lipid bilayer coating the nanoparticles, ensuring their 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 excitation.
On the basis of our preliminary in vitro and in vivo results, we intend to confirm and demonstrate that the use of bacteria naturally producing lipid-coated magnetite crystals is a very promising methodological improvement to obtain a new class of theranostic agents for cerebral pathologies. During the course of this 4-year project, magnetosomes will be genetically functionalized with relevant peptides or proteins able to interact with one physiological target of biomedical interest (human cerebral tumors implemented in a rodent model). These functionalized magnetic nanoparticles will be characterized in high-field MRI for their contrasting proprieties and their ability to interact in vivo with their targets in the rodent brain, using validated ultra-sound protocols to open the blood-brain barrier (BBB) for the passage of the theranostic agent. The increased sensitivity of the magnetosomes combined to high-field MRI would allow a more precise localization of the tumoral cells with lower doses of the agent. The development of a localized treatment in brain by hyperthermia, assisted by MRI-based localization, will be entrusted to NANOBACTERIE, the industrial partner that develops thermotherapy for cancer treatment with non-functionnalized magnetosomes (world patent). In addition to the demonstration of a proof-of-concept that can be extended to other pathologies, we will record detailed physiological data on this animal model (toxicity, biodistribution and immunogenicity) that are absolutely needed to decide further translation to human health. The deliverable of MEFISTO is a non-toxic, functionalized nano-object allowing the diagnostic of cerebral tumors by high-field MRI and their treatment by magnetic hyperthermia. Six main Tasks are identified, each one of these coordinated by one Partner of the consortium.
There is a very good complementarity between the Partners as each one is in charge of one phase of the development of the theranostic agent: the design and the production of the targeted biogenic nano-magnet is entrusted to Partner 1, now a French leading team in magnetotactic bacteria studies; the high-field MRI diagnostics is developed by Partner 2, a world leader in high-field MR imaging of the brain; finally the therapeutics is in the hands of a French biotech company whose invention in the field of brain cancer thermotherapy is protected by a world patent. The association with Partner 3 allows the in vivo studies of critical parameters such as the biodistribution, the toxicity and immunogenicity of such a novel class of targeted nanoparticles. The pathological model in rodents is common to all partners; furthermore preliminary results have already been obtained in vitro and in vivo by the academic Partners, demonstrating a fruitful collaboration that will be reinforced in the MEFISTO proposal.