Sour Angélique, Jenni Sébastien, Ortí-Suárez Ana, Schmitt Julie, Heitz Valérie, Bolze Frédéric, Loureiro de Sousa Paulo, Po Chrystelle, Bonnet Célia S, Pallier Agnès, Tóth Éva, Ventura Barbara
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.
CAMB, UMR 7199, UdS/CNRS, Faculté de Pharmacie, Université de Strasbourg , 74 route du Rhin, 67401 Illkirch, France.
Inorg Chem. 2016 May 2;55(9):4545-54. doi: 10.1021/acs.inorgchem.6b00381. Epub 2016 Apr 13.
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.
合成了一种用于磁共振成像（MRI）和光动力疗法（PDT）的分子诊疗剂，它由四个与中四苯基卟啉核相连的GdDTTA配合物（DTTA(4-) = 二亚乙基三胺-N,N,N″,N″-四乙酸）及其钇（III）类似物组成。采用多种物理化学方法对钆（III）共轭物1作为MRI造影剂和光敏剂进行了表征。在20 MHz和25 °C下于H2O中测得的质子弛豫率，每个钆中心的r1 = 43.7 mmol(-1) s(-1)，是报道的中等尺寸双水合钆（III）基造影剂中最高的，这可能与分子的刚性有关。该配合物在H2O中的单线态氧量子产率也很高，ϕΔ = 0.45，与中四磺化卟啉相似。我们还证明了钆（III）共轭物能够以低细胞毒性穿透癌细胞。在低微摩尔浓度下孵育后，评估了其对Hela细胞的光毒性，适度光照（21 J cm(-2)）诱导50%的细胞死亡。总之，这些结果证明了这种共轭物作为MRI和PDT诊疗剂的巨大潜力。
