Ruthenium complexes have been recently reported as potential chemotherapeutic agents that offer tumor selectivity and low tumor resistance. This study investigates the photochemistry and the effect of four strained photoactivatable polypyridyl ruthenium(II) complexes on non-small-cell lung cancer (A549) and triple negative breast cancer (MDA-MB-231) cells. All four ruthenium(II) complexes, [Ru(bpy)₂dmbpy]Cl₂ (C1) where (bpy = 2,2′-bipyridine and dmbpy = 6,6′-dimethyl-2,2′-bipyridine), [Ru(phen)₂dmbpy]Cl₂ (C2) where (phen = 1,10-phenanthroline), [Ru(dpphen)₂dmbpy]Cl₂ (C3) (where dpphen = 4,7-diphenyl-1,10-phenanthroline) and [Ru(BPS)₂dmbpy]Na₂ (C4) where (BPS = bathophenanthroline disulfonate) eject the dmbpy ligand upon activation by blue light. Determination of the octanol–water partition coefficient (log P) revealed that C3 was the only lipophilic complex (log P = 0.42). LC–MS/MS studies showed that C3 presented the highest cellular uptake. The cytotoxic effect of the complexes was evaluated with and without blue light activation using WST-1 kit. Data indicated that C3 exhibited the highest cytotoxicity after 72 h (MDA-MB-231, IC₅₀ = 0.73 µM; A549, IC₅₀ = 1.26 µM) of treatment. The phototoxicity indices of C3 were 6.56 and 4.64 for MDA-MB-230 and A549, respectively. Upon light activation, C3 caused significant ROS production and induced apoptosis in MDA-MB-231 cells as shown by flow cytometry. It also significantly increased Bax/Bcl2 ratio and PERK levels without affecting caspase-3 expression. C3 exhibited poor dark toxicity (IC₅₀ = 74 μM) on rat mesenchymal stem cells (MSCs). In conclusion, the physical property of the complexes dictated by the variable ancillary ligands influenced cellular uptake and cytotoxicity. C3 may be considered a promising selective photoactivatable chemotherapeutic agent that induces ROS production and apoptosis.

最近报道了钌配合物作为具有肿瘤选择性和低肿瘤抗性的潜在化学治疗剂。本研究调查了四种应变光活化聚吡啶钌 (II) 配合物对非小细胞肺癌 (A549) 和三阴性乳腺癌 (MDA-MB-231) 细胞的光化学和影响。所有四种钌 (II) 配合物，[Ru(bpy) ₂ dmbpy]Cl ₂  ( C1 ) 其中（bpy = 2,2'-联吡啶和 dmbpy = 6,6'-二甲基-2,2'-联吡啶），[ Ru(phen) ₂ dmbpy]Cl ₂  ( C2 ) 其中 (phen = 1,10-菲咯啉), [Ru(dpphen) ₂ dmbpy]Cl ₂  ( C3)（其中 dpphen = 4,7-二苯基-1,10-菲咯啉）和 [Ru(BPS) ₂ dmbpy]Na ₂ ( C4 )，其中（BPS = 红菲咯啉二磺酸盐）在被蓝光激活后会弹出 dmbpy 配体。辛醇-水分配系数 (log P ) 的测定表明C3 是唯一的亲脂性复合物 (log P  = 0.42)。LC-MS/MS 研究表明C3具有最高的细胞摄取。使用 WST-1 试剂盒在有和没有蓝光激活的情况下评估复合物的细胞毒作用。数据表明，C3在 72 小时后表现出最高的细胞毒性（MDA-MB-231，IC ₅₀  = 0.73 µM；A549，IC ₅₀ = 1.26 µM) 的处理。对于 MDA-MB-230 和 A549，C3的光毒性指数分别为 6.56 和 4.64。光激活后，C3引起显着的 ROS 产生并诱导 MDA-MB-231 细胞凋亡，如流式细胞术所示。它还显着增加了 Bax/Bcl2 比率和 PERK 水平，而不影响 caspase-3 的表达。C3 对大鼠间充质干细胞 (MSC)表现出较差的暗毒性 (IC ₅₀ = 74 μM)。总之，由可变辅助配体决定的复合物的物理性质影响细胞摄取和细胞毒性。C3 可能被认为是一种有前途的选择性光活化化学治疗剂，可诱导 ROS 产生和细胞凋亡。