Investigation of time-dependance speciation of gold-based drugs within cancer cells by cryo-X-Ray Absorption Spectroscopy

Organometallic gold complexes bearing biphenyl and diphosphine chelating ligands of the general formula [(C^C)Au(NHC)(PR3)]+ present variable antiproliferative activities depending of the PR3 ligand considered. We could evidence by cryo-XRF microscopy (ESRF, project LS-3277) the variable gold uptake and intracellular localization depending of the PR3 ligand after 4h incubation. However, we evidence by cryo-XAS spectroscopy the complete similar metabolization of each complex after the same incubation time (ESRF, project LS-3235). We now apply for beamline time at FAME UHD to perform cryo-XAS measurements on cancer cells treated with our gold complex for shorter incubation times (30 mn and 1 h) to study the kinetics of cellular metabolization in relationship with the phosphine ligand. This would represent the first structure-speciation relationship study of gold(III) complexes inside cancer cells. This project is financially supported by ITMO Cancer (project Goldspec no. 23CP039-00).