黄金对抗癌症——结果建立了金复合物的化学结构和反应性、其在细胞中的形态以及其细胞毒性之间的关系-动脉网

Gold battles cancer——Results establish a relationship between the chemical structure and reactivity of a gold complex, its speciation in the cell, and its cytotoxicity

D-Pharm 等信源发布 2025-04-09 12:47

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precious metals

贵金属

are not merely ornaments; they are also important components of pharmaceuticals, like the antitumor drug cisplatin. Recently, the search for alternatives with improved activity has begun to focus on

不仅仅是装饰品；它们也是药物的重要组成部分，比如抗肿瘤药物顺铂。最近，对于改进活性的替代物的寻找已经开始集中于

gold

黄金

. In the journal

。在期刊中

Angewandte Chemie

应用化学

, a French research team has now published the first study about the speciation and distribution of an organogold(III) complex in

，一个法国研究团队现已发表了关于有机金(III)配合物的物种形成和分布的首项研究。

cancer

癌症

cells and reveals how specially designed “organogold” complexes might open exciting avenues for fighting cancer.

细胞并揭示了特别设计的“有机金”复合物如何可能为抗癌开辟令人兴奋的新途径。

Gold has a unique electronic structure giving it exceptional chemical traits that translate into subtle interactions with biological molecules. Yet, to date, we have little information about how gold(III) complexes with antitumor activity behave in a biological environment. Do they change? Are they reduced to gold (I) or metallic gold? Where in the cell do they attack? Researchers led by Benoît Bertrand, Michèle Salmain, Sylvain Bohic, and Jean-Louis Hazemann at Sorbonne Université, the Université Grenoble Alpes, CNRS, INSERM, and the European Synchrotron Research Facility, have now carried out a comprehensive study on the chemical reactivity and antitumor activity of various gold(III) complexes.

黄金具有独特的电子结构，赋予其卓越的化学特性，这些特性转化为与生物分子的微妙相互作用。然而，迄今为止，我们对具有抗肿瘤活性的金(III)配合物在生物环境中的行为知之甚少。它们会发生变化吗？它们会被还原为金(I)或金属金吗？它们在细胞中攻击哪里？由索邦大学、格勒诺布尔阿尔卑斯大学、CNRS、INSERM和欧洲同步辐射设施的贝努瓦·贝特朗、米歇尔·萨尔曼、西尔万·博伊奇和让-路易·哈泽曼领导的研究人员，现已对各种金(III)配合物的化学反应性和抗肿瘤活性进行了全面研究。

They used a combination of different methods based on synchrotron X-ray radiation—very intensive, bundled flashes of light produced in particle accelerators..

他们使用了基于同步加速器X射线辐射的不同方法的组合——这是在粒子加速器中产生的非常强烈、集中的光闪。

Common to all the complexes they examined (cationic biphenyl gold(III) complexes with aryl, alkyl, and diphosphine helper ligands, known as [(C^C)Au(P^P)]

他们研究的所有复合物都具有共同点（带有芳基、烷基和二膦辅助配体的阳离子联苯金(III)复合物，称为[(C^C)Au(P^P)]）。

cations) is a gold atom bonded to two carbon atoms of the first ligand and two phosphorus atoms of the second, clasping like two sets of tongs. The analyses demonstrate that all the complexes examined were stable in both cell-free environments and inside lung cancer cells. They were not reduced and did not release their ligands to form new bonds..

金原子与第一个配体的两个碳原子和第二个配体的两个磷原子键合，形成类似两把钳子的结构。分析表明，所有被检测的复合物在无细胞环境和肺癌细胞内部都保持稳定，既没有被还原，也没有释放其配体形成新的键。

The complexes were demonstrated to be toxic against tumor cells. A “dppe complex” (biphenyl gold(III) complex with 1,2-diphenylphosphinoethane (dppe) ligand) was the most active. The team used a special setup of synchrotron cryo-X-ray nanoanalysis to “map” elements including gold in frozen-hydrated lung cancer cells with nanometer-scale resolution and locate the dppe complex.

这些复合物被证明对肿瘤细胞具有毒性。其中，“dppe复合物”（含1,2-二苯基膦乙烷（dppe）配体的联苯金(III)复合物）活性最强。研究团队利用同步辐射低温X射线纳米分析的特殊设置，以纳米级分辨率“绘制”包括金在内的元素图谱，并定位了冷冻水合肺癌细胞中的dppe复合物。

It was found to accumulate selectively in the mitochondria, the “powerhouses” of the cells. The advantage of this method is that no labeling, which could distort the result, is needed. This gives scientists a unique clarity when examining cells in their near-native state at the nanoscale..

它被发现会选择性地在线粒体中积累，线粒体是细胞的“动力源”。这种方法的优势在于不需要可能扭曲结果的标记。这使得科学家在以纳米级尺度观察接近天然状态的细胞时，能够获得独特的清晰度。

By using X-ray absorption spectroscopic methods, the team obtained important information about the valency, geometry, and oxidation state of the gold atom in the complex. These indicate that the antitumor activity of the gold complexes primarily stems from the native cationic species (the [(C^C)Au(P^P)].

通过使用X射线吸收光谱方法，团队获得了关于该络合物中金原子的价态、几何结构和氧化态的重要信息。这些信息表明，金络合物的抗肿瘤活性主要源于原始的阳离子物种（即[(C^C)Au(P^P)]）。

cations). It probably results from interactions between the whole complex and specific biological molecules, whose function is disrupted. This differentiates these drug candidates from other, differently structured gold complexes, which generally trigger cell death through direct coordination of the gold center with biomolecules.

它可能源于整个复合物与特定生物分子之间的相互作用，这些生物分子的功能受到干扰。这使得这些药物候选物不同于其他结构不同的金配合物，后者通常通过金中心与生物分子的直接配位来触发细胞死亡。

These results establish a relationship between the chemical structure and reactivity of a gold complex, its speciation in the cell, and its cytotoxicity..

这些结果确立了金配合物的化学结构和反应性、其在细胞中的形态分布以及其细胞毒性之间的关系。

Original publication

首次出版

Hester Blommaert, Clément Soep, Edwyn Remadna, Héloïse Dossmann, Murielle Salomé, Olivier Proux, Isabelle Kieffer, Jean‐Louis Hazemann, Sylvain Bohic, Michèle Salmain, Benoît Bertrand; 'Stability and Mitochondrial Localization of a Highly Cytotoxic Organogold(III) Complex with Diphosphine Ancillary Ligand in Lung Cancer Cells'; Angewandte Chemie International Edition, 2025-3-27.

Hester Blommaert, Clément Soep, Edwyn Remadna, Héloïse Dossmann, Murielle Salomé, Olivier Proux, Isabelle Kieffer, Jean‐Louis Hazemann, Sylvain Bohic, Michèle Salmain, Benoît Bertrand；《在肺癌细胞中具有高度细胞毒性的双膦配体有机金(III)配合物的稳定性与线粒体定位》；《应用化学国际版》，2025年3月27日。

https://www.bionity.com/en/news/1185992/gold-battles-cancer.html

https://www.bionity.com/zh/news/1185992/黄金对抗癌症.html