Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005, Paris, France.
Institut Curie, PSL University, CNRS UMR 144, 26 rue d'Ulm, 75005, Paris, France.
Chembiochem. 2020 Feb 17;21(4):531-542. doi: 10.1002/cbic.201900419. Epub 2019 Oct 22.
There is a current surge of interest in the development of novel photosensitizers (PSs) for photodynamic therapy (PDT), as those currently approved are not completely ideal. Among the tested compounds, we have previously investigated the use of Ru polypyridyl complexes with a [Ru(bipy) (dppz)] and [Ru(phen) (dppz)] scaffold (bipy=2,2'-bipyridine; dppz=dipyrido[3,2-a:2',3'-c]phenazine; phen=1,10-phenanthroline). These complexes selectively target DNA. However, because DNA is ubiquitous, it would be of great interest to increase the selectivity of our PDT PSs by linking them to a targeting vector in view of targeted PDT. Herein, we present the synthesis, characterization, and in-depth photophysical evaluation of a nanobody-containing Ru polypyridyl conjugate selective for the epidermal growth factor receptor (EGFR) in view of targeted PDT. Using ICP-MS and confocal microscopy, we could demonstrate that our conjugate has high selectivity for the EGFR receptor, which is a crucial oncological target because it is overexpressed and/or deregulated in a variety of solid tumors. However, in contrast to expectations, this conjugate was found to not produce reactive oxygen species (ROS) in cancer cells and is therefore not phototoxic.
目前，人们对新型光敏剂（PS）用于光动力疗法（PDT）的开发产生了浓厚的兴趣，因为目前批准使用的光敏剂并不完全理想。在已测试的化合物中，我们之前研究过使用具有[Ru（bipy）（dppz）]和[Ru（phen）（dppz）]支架的 Ru 多吡啶配合物（bipy=2,2'-联吡啶；dppz=二吡啶并[3,2-a：2',3'-c]吩嗪；phen=1,10-菲咯啉）。这些配合物选择性地靶向 DNA。然而，由于 DNA 无处不在，如果将其与靶向载体连接，以用于靶向 PDT，我们的 PDT PS 的选择性将会大大提高。在此，我们提出了一种含有纳米抗体的 Ru 多吡啶缀合物的合成、表征和深入的光物理评估，该缀合物针对表皮生长因子受体（EGFR），用于靶向 PDT。通过 ICP-MS 和共聚焦显微镜，我们可以证明我们的缀合物对 EGFR 受体具有高选择性，EGFR 受体是一个关键的肿瘤靶点，因为它在多种实体瘤中过度表达和/或失调。然而，与预期相反，该缀合物在癌细胞中并未产生活性氧物质（ROS），因此没有光毒性。
