钌（II）多吡啶配合物的光动力免疫治疗：在结直肠癌治疗中的应用

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2025-09-07 DOI:10.1016/j.jinorgbio.2025.113056

Lin Zhou , Huiyan Hu , Jiongbang Li , Yan Yang , Shuang Tian , Yajie Niu , Yunjun Liu , Xiandong Zeng

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引用次数: 0

摘要

本研究合成了一种新的配体2-（4-（1h -咪唑-1-基）苯基）- 1h -咪唑[4,5-f][1,10]菲罗啉（IPIP），并与顺式-[Ru（phen）₂Cl₂]·2H2O和顺式-[Ru（dip）₂Cl₂]·2H2O反应，形成了两个新的Ru（II）配合物[Ru(phen)2(IPIP)](PF6)2 （Ru1a）和[Ru(dip)2(IPIP)]（PF6)2 (Ru1b)）。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑（MTT）方法评估Ru1a和Ru1b对癌细胞和正常细胞的细胞毒性。结果表明，Ru1a在黑暗中表现出中度的细胞毒活性，Ru1b没有细胞毒活性。然而，照射1 h后，Ru1a对HCT116细胞表现出明显的细胞毒性，而Ru1b对选定的癌细胞仍然没有细胞毒活性。通过细胞摄取、线粒体定位、线粒体膜电位、细胞色素C释放和western blotting技术的进一步研究证实，Ru1a通过线粒体途径诱导HCT116细胞凋亡。rna序列分析显示Ru1a通过铁下垂导致细胞死亡。脂质过氧化产物丙二醛（MDA）水平升高，GPX4表达降低。这些发现证实了Ru1a通过铁下垂促进细胞死亡。体内抗肿瘤实验证实Ru1a在肿瘤微环境（tumor microenvironment， TME）中通过诱导免疫原性细胞死亡，激活免疫应答增强CD8+ T细胞，从而直接杀伤结直肠癌细胞，发挥抗癌活性。

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Photodynamic immunotherapy of Ruthenium(II) polypyridyl complexes: Application in the treatment of colorectal Cancer

In this study, a new ligand 2-(4-(1H-imidazol-1-yl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (IPIP) was synthesized and reacted with cis-[Ru(phen)₂Cl₂]·2H₂O and cis-[Ru(dip)₂Cl₂]·2H₂O to form two new Ru(II) complexes [Ru(phen)₂(IPIP)](PF₆)₂ (Ru1a) and [Ru(dip)₂(IPIP)](PF₆)₂ (Ru1b). The cytotoxicity of Ru1a and Ru1b against both cancer and normal cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The results revealed that Ru1a exhibits moderate and Ru1b shows no cytotoxic activity in the dark. However, after 1 h of irradiation, Ru1a exhibited significant cytotoxicity against HCT116 cells, while Ru1b still showed no cytotoxic activity toward the selected cancer cells. Further investigation via cell uptake, mitochondrial localization, mitochondrial membrane potential, cytochrome C release, and western blotting techniques confirmed that Ru1a induced apoptosis in HCT116 cells via the mitochondrial pathway. RNA-sequence assay showcases that Ru1a caused cell death through ferroptosis. The levels of lipid peroxidation product of malondialdehyde (MDA) were elevated, while the expression of GPX4 was reduced. These findings affirmed that Ru1a promotes cell death through ferroptosis. Antitumor in vivo confirmed that Ru1a exerts anticancer activity in the tumor microenvironment (TME) by inducing immunogenic cell death and activating immune responses to enhance CD8⁺ T cells, thereby directly killing colorectal cancer cells.

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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.