Significant enhancement of anticancer effect of iridium (III) complexes encapsulated in liposomes

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2024-08-24 DOI:10.1016/j.jinorgbio.2024.112706

Jiawan Yang , Xuqi Zhu , Defei Kong , Yi Wang , Yan Yang , Yunjun Liu , Hui Yin

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引用次数: 0

Abstract

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

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脂质体包裹的铱(III)复合物可显著增强抗癌效果

在这项研究中，配体 EIPP（5-乙氧基-2-(1H-咪唑并[4,5-f] [1,10] 菲罗啉-2-基)苯酚）和 [Ir(ppy)2(EIPP)](PF6)] (5a、合成了[Ir(πpy)2(EIPP)](PF6)]（5a，πpy = 2-苯基吡啶）和[Ir(πq)2(EIPP)](PF6)]（5b，πq = 1-苯基异喹啉），并将它们夹带到脂质体中，生成 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)-2,5-二苯基溴化四氮唑（MTT）评估了 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 没有显示出任何明显的细胞活性，但其脂质体包裹的 5alipo 和 5blipo 具有明显的毒性作用。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 会导致细胞色素 C 的释放，下调 Bcl-2 的表达，上调 BAX 的表达，激活 caspase 3，并下调 PARP 的表达。研究表明，5alipo 和 5blipo 可通过调节 p53 和 p21 蛋白来抑制 G2/M 期的癌细胞增殖。此外，5alipo和5blipo还能通过从LC3-I到LC3-II的调整诱导自噬，并引起铁变态反应。对 5alipo 的体内抗肿瘤活性进行了详细研究

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来源期刊

Journal of Inorganic Biochemistry 生物-生化与分子生物学

CiteScore

7.00

自引率

10.30%

发文量

336

审稿时长

41 days

期刊介绍： The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.