From Chemotherapy to Phototherapy - Changing the Therapeutic Action of a Metallo-Intercalating RuII -ReI Luminescent System by Switching its Sub-Cellular Location.
From Chemotherapy to Phototherapy - Changing the Therapeutic Action of a Metallo-Intercalating RuII -ReI Luminescent System by Switching its Sub-Cellular Location.
复制标题
从化疗到光疗 - 通过改变金属嵌入 RuII -Rel 发光系统的亚细胞位置来改变其治疗作用。
DOI：
10.1002/chem.202300617
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Saeed HK
中科院分区：
文献类型：
--
作者：
Saeed HK
报道了一种新的含RuII（dppz）和ReI（dppn）结构单元的异双核金属嵌入剂ReIRuII的合成。无细胞研究表明，该复合物与其同型M（dppz）类似物具有相似的生物物理性质，并且它也以相似的亲和力与DNA结合。然而，新报道的复合物与其母体具有非常不同的细胞内性质。在完全相反的homoleptic系统，RuII（dppz）/ReI（dppn）复杂的本质上是没有细胞毒性，但显示明显的光毒性，尽管这两个复合物显示非常相似的量子产率单线态氧敏化。光学显微镜表明，这些对比的生物学效应的原因是，而homoleptic复合物定位在细胞核中，RuII（dppz）/ReI（dppn）复合物优先在线粒体中积累。这些观察结果说明了金属基治疗电极导线中即使很小的结构变化也可以调节其作用机制。
The synthesis of a new heterodinuclear ReIRuIImetallointercalator containing RuII(dppz) and ReI(dppn) moieties is reported. Cell‐free studies reveal that the complex has similar photophysical properties to its homoleptic M(dppz) analogue and it also binds to DNA with a similar affinity. However, the newly reported complex has very different in‐cell properties to its parent. In complete contrast to the homoleptic system, the RuII(dppz)/ReI(dppn) complex is not intrinsically cytotoxic but displays appreciable phototoxic, despite both complexes displaying very similar quantum yields for singlet oxygen sensitization. Optical microscopy suggests that the reason for these contrasting biological effects is that whereas the homoleptic complex localises in the nuclei of cells, the RuII(dppz)/ReI(dppn) complex preferentially accumulates in mitochondria. These observations illustrate how even small structural changes in metal based therapeutic leads can modulate their mechanism of action.