In this study, ligands 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline (PIP), 2-(2-nitrophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (NPIP), 2-(2-nitronaphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (NNIP) and their iridium(III) metal compounds [Ir(ppy)₂(PIP)](PF₆) (ppy = 2-phenylpyridine, 1a), [Ir(ppy)₂(NPIP)](PF₆) (1b), [Ir(ppy)₂(NNIP)](PF₆) (1c) were designed and synthesized. The anti-cancer activities of 1a, 1b and 1c on BEL-7402, HepG2, SK-Hep1 and non-cancer LO2 were detected using MTT method. 1a shows moderate, 1b and 1c display low or no anti-cancer activities. To elevate the anti-cancer effectiveness, encapsulating the compounds 1a, 1b and 1c into the ordinary or targeted liposomes to produce 1alip, 1blip, 1clip, or targeted 1aTlip, 1bTlip and 1cTlip. The IC₅₀ values of 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip against HepG2 cells are 7.9 ± 0.1, 8.6 ± 0.2, 16.9 ± 0.5, 5.9 ± 0.2, 7.3 ± 0.1 and 9.7 ± 0.7 μM, respectively. Specifically, the anti-tumor activity assays in vivo found that the inhibitory rates are 23.24 % for 1a, 61.27 % for 1alip, 76.06 % for 1aTlip. It is obvious that the targeted liposomes entrapped iridium(III) compound greatly enhance anti-cancer efficacy. Additionally, 1alip, 1blip and 1clip or targeted 1aTlip, 1bTlip and 1cTlip can effectively restrain the cell colony and proliferation in the G0/G1 period. 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip can increase reactive oxygen species (ROS) concentration, arouse a decline in the mitochondrial membrane potential and promote Ca²⁺ release. RNA-sequence was applied to examine the signaling pathways. Taken together, the liposomes or targeted liposomes encapsulated compounds trigger cell death by way of apoptosis, autophagy, ferroptosis, disruption of mitochondrial function and PI3K/AKT/mTOR signaling pathways.

在本研究中，配体 2-苯基-1H-咪唑并[4,5-f][1,10]菲咯啉 (PIP)、2-(2-硝基苯基)-1H-咪唑并[4,5-f][1、 10]菲咯啉 (NPIP)、2-(2-硝基萘-1-基)-1H-咪唑并[4,5-f][1,10]菲咯啉 (NNIP) 及其铱(III)金属化合物 [Ir(ppy) ) ₂ (PIP)](PF ₆ ) (ppy = 2-苯基吡啶, 1a), [Ir(ppy) ₂ (NPIP)](PF ₆ ) (1b), [Ir(ppy) ₂ (NNIP)](PF ₆ ) (1c) 被设计和合成。采用MTT法检测1a、1b和1c对BEL-7402、HepG2、SK-Hep1和非癌LO2的抗癌活性。 1a显示中等抗癌活性，1b和1c显示低抗癌活性或无抗癌活性。为了提高抗癌效果，将化合物1a、1b和1c封装到普通或靶向脂质体中，制成1alip、1blip、1clip或靶向1aTlip、1bTlip和1cTlip。 1alip、1blip、1clip、1aTlip、1bTlip 和 1cTlip 对 HepG2 细胞的IC ₅₀值分别为 7.9 ± 0.1、8.6 ± 0.2、16.9 ± 0.5、5.9 ± 0.2、7.3 ± 0.1 和 9.7 ± 0.7 μM。具体而言，体内抗肿瘤活性测定发现，1a的抑制率为23.24%，1alip的抑制率为61.27%，1aTlip的抑制率为76.06%。很明显，包埋铱(III)化合物的靶向脂质体大大增强了抗癌功效。另外，1alip、1blip、1clip或靶向1aTlip、1bTlip、1cTlip可有效抑制G0/G1期细胞集落和增殖。 1alip、1blip、1clip、1aTlip、1bTlip和1cTlip可以增加活性氧(ROS)浓度，引起线粒体膜电位下降并促进Ca ²⁺释放。 应用RNA序列来检查信号传导途径。总而言之，脂质体或靶向脂质体封装的化合物通过细胞凋亡、自噬、铁死亡、线粒体功能破坏和 PI3K/AKT/mTOR 信号通路触发细胞死亡。