Three iridium(III) complexes [Ir(ppy)2(CPIP)](PF6) (Ir-1, ppy = 2-phenylpyridine, CPIP = 2-(4-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(DCPIP)](PF6) (Ir-2, DCPIP = 2-(3,4-dichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(TCPIP)](PF6) (Ir-3, TCPIP = 2,3,5-trichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The complexes Ir-1, Ir-2 and Ir-3 were encapsulated in liposomes to form Ir-1-Lipo, Ir-2-Lipo and Ir-3-Lipo. Morphology, size distribution, and zeta potential of liposomes were examined by transmission electron microscopy (TEM) and Zetasizer. The cytotoxic activity in vitro of Ir-1, Ir-2 and Ir-3 against cancer A549, HTC-116, HepG2, BEL-7402, Eca-109, B16, HeLa SGC-7901 and normal NIH3T3 cells was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. Ir-2 and Ir-3 show no cytotoxic activity against the selected cancer cells, and Ir-1 displays moderate cytotoxic effect on the cell growth in A549 cells. However, Ir-1, Ir-2 and Ir-3 were encapsulated in liposomes, the cytotoxic activity was greatly enhanced. In particular, Ir-1-Lipo and Ir-2-Lipo can effectively inhibit the cell growth in A549 cells with a low IC50 value of 3.1 ± 0.3 and 1.2 ± 0.4 μM. The apoptosis was assayed by flow cytometry. Ir-1, Ir-2 and Ir-3 reveal weak apoptotic effect, whereas Ir-1-Lipo, Ir-2-Lipo and Ir-3-Lipo induce an apoptotic percentage of 55.6%, 69.3% and 16.7% in A549 cells, respectively. Specially, in the assay of antitumor activity in vivo, the inhibiting percentage of tumor growth induced by Ir-2 is 27.65%, while inhibiting percentage of tumor growth caused by Ir-2-Lipo is 57.45%. Obviously, the liposomes can enhance anticancer activity in vitro and in vivo compared with the complexes. The results show that the iridium(III) complexes encapsulated liposomes induce apoptosis in A549 cells through ROS-mediated lysosome-mitochondria dysfunction pathway and target the microtubules.

中文翻译：

---

脂质体包裹的铱（III）聚吡啶基复合物可增强体内和体外的抗癌活性。

三种铱（III）配合物[Ir（ppy）2（CPIP）]（PF6）（Ir-1，ppy = 2-苯基吡啶，CPIP = 2-（4-氯苯基）-1H-咪唑[4,5-f] [1,10]菲咯啉），[Ir（ppy）2（DCPIP）] [PF6）（Ir-2，DCPIP = 2-（3,4-二氯苯基）-1H-咪唑[4,5-f] [1 ，10]菲咯啉）和[Ir（ppy）2（TCPIP）]（PF6）（Ir-3，TCPIP = 2,3,5-三氯苯基）-1H-咪唑并[4,5-f] [1,10]菲咯啉）的合成和表征。将复合物Ir-1，Ir-2和Ir-3包裹在脂质体中以形成Ir-1-Lipo，Ir-2-Lipo和Ir-3-Lipo。通过透射电子显微镜（TEM）和Zetasizer检查脂质体的形态，大小分布和Zeta电位。通过3-评估Ir-1，Ir-2和Ir-3对癌症A549，HTC-116，HepG2，BEL-7402，Eca-109，B16，HeLa SGC-7901和正常NIH3T3细胞的体外细胞毒活性（4,5-二甲基噻唑-2-基）-2，5-联苯溴化四唑（MTT）方法。Ir-2和Ir-3对选定的癌细胞没有细胞毒活性，Ir-1对A549细胞的细胞生长有中等的细胞毒作用。然而，Ir-1，Ir-2和Ir-3被包裹在脂质体中，细胞毒性活性大大增强。尤其是，Ir-1-Lipo和Ir-2-Lipo可以有效抑制A549细胞中的细胞生长，其IC50值为3.1±0.3和1.2±0.4μM。通过流式细胞术测定细胞凋亡。Ir-1，Ir-2和Ir-3显示出弱的凋亡作用，而Ir-1-Lipo，Ir-2-Lipo和Ir-3-Lipo诱导A549细胞凋亡百分比分别为55.6％，69.3％和16.7％。 ， 分别。特别地，在体内抗肿瘤活性的测定中，Ir-2诱导的肿瘤生长的抑制百分比为27.65％，而抑制Ir-2-Lipo引起的肿瘤生长百分比为57.45％。显然，与复合物相比，脂质体在体外和体内均可增强抗癌活性。结果表明，铱（III）复合物包裹的脂质体通过ROS介导的溶酶体-线粒体功能障碍途径诱导A549细胞凋亡，并靶向微管。