Karges Johannes, Yempala Thirumal, Tharaud Mickaël, Gibson Dan, Gasser Gilles
Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005, Paris, France.
Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, 91120, Jerusalem, Israel.
Angew Chem Int Ed Engl. 2020 Apr 27;59(18):7069-7075. doi: 10.1002/anie.201916400. Epub 2020 Mar 11.
Pt complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt -Ru conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt centre is reduced to Pt and the axial ligands including the Ru complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.
铂配合物常用于治疗癌症。为了减少其副作用并改善其药理性质，铂配合物正被开发为可通过癌细胞内还原作用而激活的前药候选物。与此同时，钌多吡啶配合物因其具有吸引人的特性，作为用于光动力疗法的光敏剂而备受关注。在本文中，提出了一种新型的铂-钌共轭物，它将癌症激活化疗与光动力疗法相结合。进入癌细胞后，铂中心被还原为铂，包括钌配合物和苯丁酸盐在内的轴向配体被释放。由于每种成分都有其各自的靶点，该共轭物在各种（耐药）二维单层癌细胞和三维多细胞肿瘤球体中，在低纳摩尔范围内对高达595 nm的辐射具有（光）细胞毒性值，从而发挥多靶点和多作用效应。
