Antitumor activity studies of iridium (III) polypyridine complexes-loaded liposomes against gastric tumor cell in vitro

Authors：Xie, Fu-Li; Huang, Zhi-Tong; Bai, Lan; Zhu, Jian-Wei; Xu, Hui-Hua; Long, Qing-Qin; Guo, Qi-Feng^*; Wu, Yong^*; Liu, Si-Hong^*

Source：Journal of Inorganic Biochemistry, 2021, 225: 111603.

DOI：10.1016/j.jinorgbio.2021.111603

• Iridium (III) complexes
• Liposomes
• Mitochondria
• Apoptosis
• Antitumor
• Gastric cancer

Two iridium (III) polypyridine complexes [Ir(ppy)(2)(BIP)]PF6 (ppy = 2 phenylpyridine, BIP = 2 biphenyl-1H-imidazo [4,5-f] [1,10]phenanthroline, Ir1), Pr(piq)(2)(BIP)]PF6 (piq = 1-phenylisoquinoline, Ir2) and their liposomes Ir1lipo and Ir2lipo were synthesized and characterized. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenylte-trazolium 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 IC50 value of 5.8 +/- 0.2 mu M, 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.

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