在本研究中，配体 EIPP (5-乙氧基-2-(1H-咪唑并[4,5-f] [1,10]菲咯啉-2-基)苯酚) 和 [Ir(ppy)2(EIPP)](合成了 PF6)] (5a, ppy = 2-苯基吡啶) 和 [Ir(piq)2(EIPP)](PF6)] (5b, piq = 1-苯基异喹啉)，并将它们包埋到脂质体中以产生 5alipo 和 5blipo。通过 HRMS、NMR、UV-vis 和 IR 对 5a 和 5b 进行了表征。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 评估 5a、5b、5alipo 和 5blipo 对癌细胞和非癌细胞的细胞毒性。 MTT分析表明5a和5b没有表现出任何显着的细胞活性，但其脂质体封装的5alipo和5blipo具有显着的毒性作用。通过研究细胞摄取、线粒体定位、线粒体膜电位、细胞色素C、谷胱甘肽（GSH）、丙二醛（MDA）和蛋白质免疫印迹，探讨了5alipo、5blipo诱导细胞凋亡的机制。结果表明，5alipo和5blipo引起细胞色素C的释放，下调Bcl-2的表达，上调BAX的表达，激活caspase 3，下调PARP的表达。结果表明，5alipo和5blipo可以通过调节p53和p21蛋白抑制G2/M期癌细胞增殖。此外，5alipo 和 5blipo 通过从 LC3-I 调整为 LC3-II 诱导自噬，并引起铁死亡。详细检查了 5alipo 的体内抗肿瘤活性。版权所有 © 2024 Elsevier Inc. 保留所有权利。

In this study, the ligand EIPP (5-ethoxy-2-(1H-imidazo[4,5-f] [1,10] phenanthrolin-2-yl)phenol) and [Ir(ppy)2(EIPP)](PF6)] (5a, ppy = 2-phenylpyridine) and [Ir(piq)2(EIPP)](PF6)] (5b, piq = 1-phenylisoquinoline) were synthesized and they were entrapped into liposomes to produce 5alipo and 5blipo. 5a and 5b were characterized via HRMS, NMR, UV-vis and IR. The cytotoxicity of 5a, 5b, 5alipo and 5blipo on cancer and non-cancer cells was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). MTT assay demonstrated that 5a and 5b did not show any significant cellular activity but their liposome-encapsulated 5alipo and 5blipo had significant toxic effects. The mechanism of 5alipo, 5blipo-inducing apoptosis was explored by studying cellular uptake, mitochondrial localization, mitochondrial membrane potential, cytochrome C, glutathione (GSH), malondialdehyde (MDA) and protein immunoblotting. The results demonstrated that 5alipo and 5blipo caused a release of cytochrome C, downregulated the expression of Bcl-2, upregulated the expression of BAX, activated caspase 3, and downregulated PARP expression. It was shown that 5alipo and 5blipo could inhibit cancer cell proliferation in G2/M phase by regulating p53 and p21 proteins. Additionally, 5alipo and 5blipo induced autophagy through an adjustment from LC3-I to LC3-II and caused ferroptosis. The in vivo antitumor activity of 5alipo was examined in detail.Copyright © 2024 Elsevier Inc. All rights reserved.