Bioanalytical and biophysical techniques for the elucidation of the mode of action of metal-based drugs

Platinum-based drugs present one of the pillars of anticancer chemotherapy, and pharmaceuticals incorporating metals such as ruthenium, gallium, titanium and gold, some of which have already entered clinical trials, show promising features including activity against platinum-resistant tumors and/or reduced side-effects. The mode of action of these novel metallodrugs has only been partly elucidated, and even for established treatments, some questions concerning the interactions with targets such as DNA and proteins on a molecular level remain unanswered. In order to tackle the challenging problem of characterizing the behavior of metallodrugs in complex biological media and tissues in vitro and in vivo, bioanalytical and biophysical methodologies are employed. The current state of these techniques, their strengths and limitations, and the information they can provide for achieving this demanding goal, are described in this review.