Design of polyazamacrocyclic Gd3+ theranostic agents combining magnetic resonance imaging and two-photon photodynamic therapy - Université de Bretagne Occidentale
Article Dans Une Revue Inorganic Chemistry Frontiers Année : 2021

Design of polyazamacrocyclic Gd3+ theranostic agents combining magnetic resonance imaging and two-photon photodynamic therapy

Laura Abad Galán
János Kiss
György Trencsényi
Cyrille Monnereau
Gyula Tircsó
Olivier Maury

Résumé

New “all-in-one” theranostic systems, combining a magnetic resonance imaging (MRI) contrast agent with a biphotonic photodynamic therapy (2P-PDT) photosensitiser generating cytotoxic singlet oxygen, were envisaged and synthesised. They are based on azamacrocycles, regiospecifically functionalised by two-photon PDT π-conjugated dibromobenzene–picolinate photosensitisers and acetate, able to complex gadolinium(III) and allow an MRI signal. Our approach was to use two different macrocyclic platforms, tacn and pyclen, for modulating simultaneously the structures, properties and solubility of the complexes. Photophysical properties of the ligands and their gadolinium(III) complexes were fully investigated. The Gd3+–pyclen derivative showed the best water solubility and the greatest value of singlet oxygen generation of the series with ΦΔ = 0.53 enabling in vitro studies. The biological PDT activity under mono and biphotonic excitation was evaluated in human breast cancer cells (MCF-7). While a very low dark toxicity was observed, an almost total cell death was induced after only 3 successive irradiations of 1.57 s. Finally, its relaxivity was measured in a DMSO/H2O solvent mixture with r1p = 11.21 and r2p = 24.60 mM−1 s−1 at 3.0 T and T1- and T2-weighted phantom MR images were obtained highlighting a first generation of “all-in-one” PDT/MRI theranostic agents.
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Laura Abad Galán, Nadège Hamon, Christophe Nguyen, Enikő Molnár, János Kiss, et al.. Design of polyazamacrocyclic Gd3+ theranostic agents combining magnetic resonance imaging and two-photon photodynamic therapy. Inorganic Chemistry Frontiers, 2021, 8 (9), pp.2213-2224. ⟨10.1039/D0QI01519A⟩. ⟨hal-03137794⟩
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