羟基镓咔咯光动力抗肝癌的体内外活性

Improvement in Photodynamic Activity of Gallium Hydroxycorrole Towards Hepatocellular Cancer Cells in vitro and in vivo

制备了10-(4-羟基苯基)-5,15-二(五氟苯基)咔咯(1)及其金属镓配合物(1-Ga),并用分子生物技术对肝癌细胞的光动力活性进行了研究。结果表明,咔咯金属配合物的光动力活性在很大程度上取决于中心金属,镓的引入可以提高光动力抗肿瘤活性在肝癌细胞中,1-Ga在光照射下触发细胞内活性氧物种(ROS)的显著产生以及线粒体膜电位的变化,最终导致癌细胞坏死和凋亡。1-Ga对人肝癌细胞MHCC97H细胞(MHCC97H)与人肝癌细胞HepG2细胞(HepG2)的光动力半数抑制浓度在2~4μmol/L之间,而1的浓度大于4μmol/L。此类咔咯化合物表现出较高的生物相容性和光动力抗癌效率,在小鼠体内癌症模型中表现明显,与对照组相比,治疗组肿瘤组织质量下降超过70%。其作用机制可能与ROS产生后对线粒体功能影响有关。1-Ga的光动力活性明显优于1,可能是金属镓光动力产生更多ROS的结果。

10-(4-hydroxyphenyl)-5,15-bis(pentafluorophenyl)corrole(1)and its metal gallium complex(1-Ga)were prepared,and the photodynamic activity of hepatocellular carcinoma cells was studied by molecular biotechnology.The results indicated that the phototoxicity of corroles depended largely on the central metal,and gallium could enhance the photodynamic activities.In liver cancer cells,1-Ga triggered the significant production of reactive oxygen species(ROS)and the change of mitochondrial membrane potential under light irradiation,which eventually led to cancer cell necrosis and apoptosis.The half inhibitory concentration of 1-Ga on the photodynamic activity of human hepatoma cells(MHCC97H)and human hepatoma cells(HepG2)is between 2~4μmol/L,while the concentration of 1 is greater than 4μmol/L.These corroles showed high biocompatibility and photodynamic anticancer efficiency,which were obvious in mouse cancer model.Compared with the control group,the mass of tumor tissue in the treatment group decreased by more than 70%.And the mechanism may be related to the influence of ROS production on mitochondrial function.It is worth mentioning that the photodynamic activity of 1-Ga is obviously better than that of 1,which may be related to the photodynamic production of more ROS by gallium corrole.