LAUSR

Abstract Following the serendipitous discovery of the anticancer drug, cisplatin, numerous platinum(II) complexes have been synthesized and some of them, such as carboplatin, oxaliplatin, nedaplatin, heptaplatin and lobaplatin, have been clinically approved either locally or worldwide. Since these drugs are structurally related to cisplatin, the unfortunate problems that are associated with cisplatin are more or less the same for them. To overcome these problems, octahedral, low-spin d6 and coordinatively saturated Pt(IV) complexes have been examined because of their substitution inertness towards off-target biomolecules. Owing to the availability of bio-reducing agents, mainly proteins, in all cell types, Pt(IV) prodrugs can be reduced to their cytotoxic active Pt(II) analogues in both cancer and normal cells. However, prolonged hydrolysis and less stability against bio-reducing agents are problems still to be overcome. To address the passive activation of Pt(IV) prodrugs, the choice of photoactivated Pt(IV) prodrugs seems to be a promising chemotherapeutic strategy. Therefore, iodo-based photolabile Pt(IV) complexes which, upon light exposure, undergo photolytic reactions to give active Pt(II) species have been developed. Unfortunately, these complexes had to be later discarded because of their low stability in the dark. Eventually, azido-based complexes with enhanced stability in the dark were developed. The selective photoactivation of these photolabile azido-based Pt(IV) prodrugs has dramatically opened up new avenues of research aimed at overcoming the problems associated with chemotherapeutic drug delivery by incorporating different polymers, biological target molecules, permeation enhancers or nanoparticles. These photolabile complexes are the focus of the present review.