A lysosome-targeted ruthenium(II) polypyridyl complex as photodynamic anticancer agent

Polypyridyl ruthenium complexes as novel photosensitizers had drawn attention due to its high selectivity towards cancer cells and low toxicity to normal cells. Herein, we synthesized a lysosome-targeted polypyridyl ruthenium complex Rhein-Ru(bpy)₃ (bpy = 2,2'-bipyridine, rhein = 4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid), tethering with the Chinese medicine herb rhein. Rhein-Ru(bpy)₃ exhibited high phototoxicity with short time of irradiation against tumor cell lines with the IC₅₀ value of 2.4- 8.7 μM, and higher cytotoxicity against cisplatin-resistant A2780 cell lines, suggesting that Rhein-Ru(bpy)₃ could overcome the cisplatin resistance. Moreover, Rhein-Ru(bpy)₃ displayed low cytotoxicity towards cell lines in dark incubation, which was beneficial to reduce the toxic side effects towards normal cell lines. Besides, the confocal imaging and western blotting assay results suggested that Rhein-Ru(bpy)₃ could induce cancer cell death through the autophagy pathway. These results inspired us that lysosome-targeted photosensitizers based on ruthenium complexes showed great potential for photodynamic therapy (PDT) application in cancer treatment.