Schmitt Julie, Heitz Valérie, Sour Angélique, Bolze Frédéric, Kessler Pascal, Flamigni Lucia, Ventura Barbara, Bonnet Célia S, Tóth Éva
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.
Chemistry. 2016 Feb 18;22(8):2775-86. doi: 10.1002/chem.201503433. Epub 2016 Jan 21.
The convergent synthesis and characterization of a potential theranostic agent, DPP-ZnP-GdDOTA, which combines a diketopyrrolopyrrole-porphyrin component DPP-ZnP as a two-photon photosensitizer for photodynamic therapy (PDT) with a gadolinium(III) DOTA complex as a magnetic resonance imaging probe, is presented. DPP-ZnP-GdDOTA has a remarkably high longitudinal water proton relaxivity (19.94 mm(-1) s(-1) at 20 MHz and 25 °C) for a monohydrated molecular system of this size. The Nuclear Magnetic Relaxation Dispersion (NMRD) profile is characteristic of slow rotation, related to the extended and rigid aromatic units integrated in the molecule and to self-aggregation occurring in aqueous solution. The two-photon properties were examined and large two-photon absorption cross-sections around 1000 GM were determined between 910 and 940 nm in DCM with 1 % pyridine and in DMSO. Furthermore, the new conjugate was able to generate singlet oxygen, with quantum yield of 0.42 and 0.68 in DCM with 1 % pyridine and DMSO, respectively. Cellular studies were also performed. The DPP-ZnP-GdDOTA conjugate demonstrated low dark toxicity and was able to induce high one-photon and moderate two-photon phototoxicity on cancer cells.
本文介绍了一种潜在的诊疗试剂DPP-ZnP-GdDOTA的收敛合成与表征，该试剂将二酮吡咯并吡咯-卟啉组分DPP-ZnP作为光动力疗法（PDT）的双光子光敏剂，与钆（III）DOTA配合物作为磁共振成像探针相结合。对于这种尺寸的单水合分子体系，DPP-ZnP-GdDOTA具有非常高的纵向水质子弛豫率（在20 MHz和25°C下为19.94 mm(-1) s(-1)）。核磁共振弛豫色散（NMRD）曲线具有慢旋转的特征，这与分子中整合的扩展刚性芳香单元以及水溶液中发生的自聚集有关。研究了其双光子性质，并在含有1%吡啶的二氯甲烷和二甲基亚砜中，于910至940 nm之间测定了约1000 GM的大二光子吸收截面。此外，这种新的共轭物能够产生单线态氧，在含有1%吡啶的二氯甲烷和二甲基亚砜中，量子产率分别为0.42和0.68。还进行了细胞研究。DPP-ZnP-GdDOTA共轭物表现出低暗毒性，并且能够对癌细胞诱导高单光子和中等双光子光毒性。
