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, Unistra/CNRS, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch, France.
Inorg Chem. 2020 Oct 5;59(19):14389-14398. doi: 10.1021/acs.inorgchem.0c02189. Epub 2020 Sep 22.
With the aim of developing new molecular theranostic agents, a π-extended Zn(II) porphyrin as photosensitizer for photodynamic therapy (PDT) linked to two GdDOTA-type complexes for magnetic resonance imaging (MRI) detection was synthesized. The relaxivity studies revealed a much higher relaxivity value per Gd ion for this medium sized molecule (19.32 mM s at 20 MHz and 298 K) compared to clinical contrast agents-a value which strongly increases in the presence of bovine serum albumin, reaching 25.22 mM s. Moreover, the photophysical studies showed the strong ability of the molecule to absorb light in the deep red (670 nm, ε ≈ 60000 M cm) and in the near-infrared following two-photon excitation (920 nm, σ ≈ 650 GM). The conjugate is also able to generate singlet oxygen, with a quantum yield of 0.58 in DMSO. Promising results were obtained in cellular studies, demonstrating that the conjugate is internalized in HeLa cells at micromolar concentration and leads to 70% of cell death following 30 min irradiation at 660 nm. These results confirm the potential of the designed molecule as an imaging and therapeutic agent.
为了开发新的分子治疗诊断试剂，我们合成了一种作为光动力治疗（PDT）光敏剂的π-扩展锌(II)卟啉，它与两个 GdDOTA 型配合物相连，用于磁共振成像（MRI）检测。弛豫率研究表明，与临床对比剂相比，这种中等大小分子的每个 Gd 离子的弛豫率更高（在 20 MHz 和 298 K 时为 19.32 mM s）-在牛血清白蛋白存在下，该值会大幅增加，达到 25.22 mM s。此外，光物理研究表明，该分子在深红光（670nm，ε≈60000 M cm）和近红外（920nm，σ≈650 GM）下具有很强的双光子激发吸收光的能力。该配合物还能够产生单线态氧，在 DMSO 中的量子产率为 0.58。细胞研究取得了有前景的结果，表明该配合物在微摩尔浓度下被 HeLa 细胞内化，并在 660nm 照射 30 分钟后导致 70%的细胞死亡。这些结果证实了设计的分子作为成像和治疗剂的潜力。
