Four Gadolinium(III) Complexes Appended to a Porphyrin: A Water-Soluble Molecular Theranostic Agent with Remarkable Relaxivity Suited for MRI Tracking of the Photosensitizer.
Fiche publication
Date publication
mai 2016
Journal
Inorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PO Chrystelle
Tous les auteurs :
Sour A, Jenni S, Ortí-Suárez A, Schmitt J, Heitz V, Bolze F, Loureiro de Sousa P, Po C, Bonnet CS, Pallier A, Tóth É, Ventura B
Lien Pubmed
Résumé
A molecular theranostic agent for magnetic resonance imaging (MRI) and photodynamic therapy (PDT) consisting of four [GdDTTA](-) complexes (DTTA(4-) = diethylenetriamine-N,N,N″,N″-tetraacetate) linked to a meso-tetraphenylporphyrin core, as well as its yttrium(III) analogue, was synthesized. A variety of physicochemical methods were used to characterize the gadolinium(III) conjugate 1 both as an MRI contrast agent and as a photosensitizer. The proton relaxivity measured in H2O at 20 MHz and 25 °C, r1 = 43.7 mmol(-1) s(-1) per gadolinium center, is the highest reported for a bishydrated gadolinium(III)-based contrast agent of medium size and can be related to the rigidity of the molecule. The complex displays also a remarkable singlet oxygen quantum yield of ϕΔ = 0.45 in H2O, similar to that of a meso-tetrasulfonated porphyrin. We also evidenced the ability of the gadolinium(III) conjugate to penetrate in cancer cells with low cytotoxicity. Its phototoxicity on Hela cells was evaluated following incubation at low micromolar concentration and moderate light irradiation (21 J cm(-2)) induced 50% of cell death. Altogether, these results demonstrate the high potential of this conjugate as a theranostic agent for MRI and PDT.
Mots clés
Cell Death, drug effects, Coordination Complexes, chemical synthesis, Gadolinium, chemistry, HeLa Cells, Humans, Light, Lysosomes, metabolism, Magnetic Resonance Imaging, Photosensitizing Agents, chemical synthesis, Porphyrins, chemical synthesis, Proton Magnetic Resonance Spectroscopy, Solubility, Theranostic Nanomedicine, Water, chemistry, Yttrium, chemistry
Référence
Inorg Chem. 2016 05 2;55(9):4545-54