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Design, synthesis and optimization of Fe(III) based porphyrins for use as next-generation MRI probes

Project description

Advancing MRI safety with iron-based contrast agents

Magnetic resonance imaging (MRI) is essential for early disease diagnosis and treatment monitoring. However, the gadolinium-based contrast agents (Gd-CAs) used in MRI raise significant safety and environmental concerns. The challenge lies in finding a viable alternative that is both effective and non-toxic. Iron (Fe(III)) porphyrins show promise, but are hindered by issues like μ-oxo-dimer formation, which reduces their efficacy. With the support of the Marie Skłodowska-Curie Actions programme, the PorphIRON project aims to overcome these limitations by developing new iron-based contrast agents. By optimising the structure of Fe(III) porphyrins, PorphIRON will enhance their stability and effectiveness while ensuring biocompatibility. This project combines advanced porphyrin chemistry with computational studies and MRI expertise to create safe, high-performance contrast agents for future clinical use.

Objective

Magnetic resonance imaging (MRI) plays a pivotal role in early diagnosis and therapy follow-up of many diseases. The substitution of current Gd-based MRI contrast agents (CA), which raise both safety and environmental concerns, is one of todays most important challenges in imaging-related chemistry. High complex stabilities and inertness attainable with Fe(III) make it a high potential alternative to Gd. Porphyrins have met great clinical success, exhibit biocompatibility, stable metal complexes and easy structural modulation., but formation of -oxo-dimers in Fe(III) porphyrins (FePo) reduces their relaxation efficacy. PorphIRON will tackle these limitations and develop new families of biocompatible FePo fine-tuned for MRI use. PorphIRON will focus on structural optimization to i) maintain the oxidation and the high spin state of Fe(III), yielding relaxation effect comparable to clinical CA, and ii) adjust physicochemical properties to preserve biocompatibility. To achieve this, PorphIRON will rely on a synergic combination of the ERs experience in porphyrin chemistry and computational studies with that of the supervisor in MRI CA development, and an iterative approach with: i) initial synthesis of newly designed FePo, followed by their physicochemical and biological evaluation; ii) computational rationalization of the experimental results and prediction of new optimized structures; iii) second-round optimized FePo synthesis and characterization. PorphIRON will deliver fully characterized, stable, biocompatible and high efficacy FePos with preliminary preclinical in vivo MRI validation, thereby actively contributing to the implementation of next-generation non-toxic CA in clinic. PorphIRON will strengthen ERs experience in organic synthesis, computational chemistry, while significantly expanding his knowledge to CA development and preclinical MRI. It will expand his career perspectives and open new opportunities in the emerging field of theragnostics.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 195 914,88
Total cost

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