French Researchers Investigate Gold(III) Complexes for Cancer Treatment

A study published in Angewandte Chemie explores the chemical behavior and antitumor activity of gold(III) complexes in cancer cells, offering insights into their potential as therapeutic agents. Gold’s unique electronic structure enables subtle interactions with biological molecules, but little is known about how gold(III) complexes behave in biological environments. Researchers from Sorbonne Université, Université Grenoble Alpes, CNRS, INSERM, and the European Synchrotron Research Facility conducted a comprehensive analysis of these complexes using advanced synchrotron X-ray techniques.

The study focused on cationic biphenyl gold(III) complexes with aryl, alkyl, and diphosphine ligands, known as [(C^C)Au(P^P)]⁺ cations. These complexes feature a gold atom bonded to two carbon atoms and two phosphorus atoms, forming a stable structure resembling tongs. Tests revealed that the complexes remained chemically stable in both cell-free environments and lung cancer cells, without reduction or ligand release.

Among the complexes studied, the dppe complex (gold(III) complex with 1,2-diphenylphosphinoethane ligand) demonstrated the highest toxicity against tumor cells. Using synchrotron cryo-X-ray nanoanalysis, researchers mapped the dppe complex within frozen-hydrated lung cancer cells at nanometer resolution. The complex selectively accumulated in mitochondria, disrupting cellular function without requiring labeling that might alter results.

Further analysis using X-ray absorption spectroscopy provided detailed information about the valency, geometry, and oxidation state of the gold atom. Findings suggest that the antitumor activity stems from interactions between the intact cationic species and specific biological molecules. This mechanism differs from other gold complexes that induce cell death through direct coordination with biomolecules.

The study establishes a link between the chemical structure of gold complexes, their behavior in cells, and their cytotoxicity, paving the way for further research into their therapeutic potential against cancer.