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一种具有二膦辅助配体的高细胞毒性有机金（III）配合物在肺癌细胞中的稳定性和线粒体定位

Stability and Mitochondrial Localization of a Highly Cytotoxic Organogold(III) Complex with Diphosphine Ancillary Ligand in Lung Cancer Cells.

作者信息

Blommaert Hester, Soep Clément, Remadna Edwyn, Dossmann Héloïse, Salomé Murielle, Proux Olivier, Kieffer Isabelle, Hazemann Jean-Louis, Bohic Sylvain, Salmain Michèle, Bertrand Benoît

机构信息

Institut Néel CNRS, Université Grenoble Alpes, 25 Avenue des Martyrs, Grenoble, 38042, France.

BM16/FAME beamline, The European Synchrotron Radiation Facility, 71 avenue des Martyrs, Grenoble, F-38000, France.

出版信息

Angew Chem Int Ed Engl. 2025 May 26;64(22):e202422763. doi: 10.1002/anie.202422763. Epub 2025 Mar 27.

DOI:10.1002/anie.202422763
PMID:40084569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12105710/
Abstract

We present a comprehensive study on the chemical reactivity in the gas phase, with amino acids and peptides, and in the cell, the anticancer activity and localization of a series of seven cationic biphenyl gold(III) complexes with aryl, alkyl, and chiral diphosphine ancillary ligands. Despite some structural differences, all the complexes similarly featured high stability toward reduction or ligand exchange in cell-free conditions. The biphenyl Au(III) complex including the 1,2-diphenylphosphinoethane (dppe) ligand manifested the same high stability in a cellular setting, as attested by a combination of cryo-Synchrotron Radiation-X-Ray Fluorescence (cryo-SR-XRF) nano-imaging and cryo-Synchrotron Radiation-X-ray Absorption Spectroscopy (cryo-SR-XAS) measurements. Tandem cryo-SR-XRF elemental mapping and confocal fluorescence microscopy demonstrated the selective accumulation of the dppe complex in mitochondria. This represents the first study of the speciation and distribution of an organogold(III) complex in cancer cells.

摘要

我们对一系列七种带有芳基、烷基和手性二膦辅助配体的阳离子联苯金（III）配合物在气相中与氨基酸和肽的化学反应性，以及在细胞中的抗癌活性和定位进行了全面研究。尽管存在一些结构差异，但所有配合物在无细胞条件下对还原或配体交换都具有相似的高稳定性。包括1,2-二苯基膦基乙烷（dppe）配体的联苯金（III）配合物在细胞环境中也表现出同样的高稳定性，这通过低温同步辐射X射线荧光（cryo-SR-XRF）纳米成像和低温同步辐射X射线吸收光谱（cryo-SR-XAS）测量得到证实。串联低温SR-XRF元素映射和共聚焦荧光显微镜显示dppe配合物在线粒体中选择性积累。这是关于有机金（III）配合物在癌细胞中的形态和分布的首次研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/2599c7bfcbfd/ANIE-64-e202422763-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/af85832fa2a2/ANIE-64-e202422763-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/a6d2e4419010/ANIE-64-e202422763-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/3afa8ab337ac/ANIE-64-e202422763-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/8b70abb23a3d/ANIE-64-e202422763-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/2599c7bfcbfd/ANIE-64-e202422763-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/af85832fa2a2/ANIE-64-e202422763-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/a6d2e4419010/ANIE-64-e202422763-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/3afa8ab337ac/ANIE-64-e202422763-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/8b70abb23a3d/ANIE-64-e202422763-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab0/12105710/2599c7bfcbfd/ANIE-64-e202422763-g001.jpg

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