title: Four Gadolinium(III) Complexes Appended to a Porphyrin: A Water-Soluble Molecular Theranostic Agent with Remarkable Relaxivity Suited for MRI Tracking of the Photosensitizer.
abstract: 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.
authors.affiliation: Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnels, Institut de Chimie de Strasbourg, CNRS/UMR 7177, Université de Strasbourg , 4 rue Blaise Pascal, 67000 Strasbourg, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Sour
authors.affiliation: Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnels, Institut de Chimie de Strasbourg, CNRS/UMR 7177, Université de Strasbourg , 4 rue Blaise Pascal, 67000 Strasbourg, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jenni
authors.affiliation: Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnels, Institut de Chimie de Strasbourg, CNRS/UMR 7177, Université de Strasbourg , 4 rue Blaise Pascal, 67000 Strasbourg, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortí-Suárez
authors.affiliation: Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnels, Institut de Chimie de Strasbourg, CNRS/UMR 7177, Université de Strasbourg , 4 rue Blaise Pascal, 67000 Strasbourg, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Schmitt
authors.affiliation: Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnels, Institut de Chimie de Strasbourg, CNRS/UMR 7177, Université de Strasbourg , 4 rue Blaise Pascal, 67000 Strasbourg, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Heitz
authors.affiliation: CAMB, UMR 7199, UdS/CNRS, Faculté de Pharmacie, Université de Strasbourg , 74 route du Rhin, 67401 Illkirch, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bolze
authors.affiliation: CNRS, ICube, FMTS, Institut de Physique Biologique, Faculté de Médecine, Université de Strasbourg , 4 rue Kirschleger, 67085 Strasbourg Cedex, France.
authors.forename: Paulo
authors.initials: P
authors.lastname: Loureiro de Sousa
authors.affiliation: CNRS, ICube, FMTS, Institut de Physique Biologique, Faculté de Médecine, Université de Strasbourg , 4 rue Kirschleger, 67085 Strasbourg Cedex, France.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Po
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, Université d'Orléans , rue Charles Sadron, CS 80054, 45071 Orléans Cedex 2, France.
authors.forename: Célia S
authors.initials: CS
authors.lastname: Bonnet
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, Université d'Orléans , rue Charles Sadron, CS 80054, 45071 Orléans Cedex 2, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Pallier
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, Université d'Orléans , rue Charles Sadron, CS 80054, 45071 Orléans Cedex 2, France.
authors.forename: Éva
authors.initials: É
authors.lastname: Tóth
authors.affiliation: Istituto ISOF-CNR , via P. Gobetti 101, 40129 Bologna, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ventura
mesh_terms: D016923:Cell Death / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D005682:Gadolinium / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008247:Lysosomes / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D011166:Porphyrins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects / Q000633:toxicity; D066244:Proton Magnetic Resonance Spectroscopy; D012995:Solubility; D000068936:Theranostic Nanomedicine; D014867:Water / Q000737:chemistry; D015019:Yttrium / Q000737:chemistry
chemical_list: D056831:Coordination Complexes; D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water; D015019:Yttrium; D005682:Gadolinium