Department of Orthopaedics, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, PR China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
J Inorg Biochem. 2021 Dec;225:111603. doi: 10.1016/j.jinorgbio.2021.111603. Epub 2021 Sep 14.
Two iridium (III) polypyridine complexes [Ir(ppy)(BIP)]PF (ppy = 2-phenylpyridine, BIP = 2-biphenyl-1H-imidazo[4,5-f][1,10]phenanthroline, Ir1), [Ir(piq)(BIP)]PF (piq = 1-phenylisoquinoline, Ir2) and their liposomes Ir1lipo and Ir2lipo were synthesized and characterized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cytotoxic activity against several cancer cells (A549, HepG2, SGC-7901, Bel-7402, HeLa) and non-cancer cell (mouse embryonic fibroblast, NIH3T3). The results showed that Ir1lipo displays the high cytotoxicity toward SGC-7901 with IC value of 5.8 ± 0.2 μM, while the complexes have no cytotoxicity toward A549, HepG2, Bel-7402 and HeLa cells. The cell colony demonstrated that the iridium (III) complexes-loaded liposomes can inhibit cell proliferation, induce cell cycle arrest at G0/G1 phase. Moreover, they also cause autophagy, induce a decrease of mitochondrial membrane potential and increase intracellular reactive oxygen species (ROS) content. These results suggest that the complexes encapsulated liposomes Ir1lipo and Ir2lipo inhibit the growth of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction and activating the PI3K (phosphoinositide-3 kinase)/ AKT (protein kinase B) signaling pathways.
合成并表征了两种铱(III) 多吡啶配合物[Ir(ppy)(BIP)]PF（ppy=2-苯基吡啶，BIP=2-联苯-1H-咪唑[4,5-f][1,10]菲咯啉，Ir1），[Ir(piq)(BIP)]PF（piq=1-苯基异喹啉，Ir2）及其脂质体 Ir1lipo 和 Ir2lipo。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法评估了对几种癌细胞（A549、HepG2、SGC-7901、Bel-7402、HeLa）和非癌细胞（小鼠胚胎成纤维细胞，NIH3T3）的细胞毒性活性。结果表明，Ir1lipo 对 SGC-7901 具有高细胞毒性，IC 值为 5.8±0.2μM，而配合物对 A549、HepG2、Bel-7402 和 HeLa 细胞没有细胞毒性。细胞集落实验表明，载铱（III）配合物的脂质体可以抑制细胞增殖，诱导细胞周期停滞在 G0/G1 期。此外，它们还能诱导自噬，降低线粒体膜电位并增加细胞内活性氧（ROS）含量。这些结果表明，包封的脂质体 Ir1lipo 和 Ir2lipo 通过 ROS 介导的线粒体功能障碍和激活 PI3K（磷酸肌醇 3 激酶）/AKT（蛋白激酶 B）信号通路抑制 SGC-7901 细胞的生长。
