A Ratiometric Fluorescent Probe for Cisplatin: Investigating the Intracellular Reduction of Platinum(IV) Prodrug Complexes

The PtIV prodrug strategy has emerged as an excellent alternative to tackle the problems associated with conventional PtII drug therapy. However, there is a lack of tools to study how this new class of PtIV drugs are processed at the cellular level. Herein, we report the first ratiometric probe for cisplatin detection and use it to investigate PtIV anticancer complexes in biological systems. The probe was able to distinguish between cisplatin and its PtIV derivatives, allowing us to probe the intracellular reduction of PtIV prodrug complexes. The correlation between the amount of active PtII species available after intracellular reduction of PtIV complexes and their cytotoxicity and the role glutathione plays in the reduction of PtIV complexes were investigated. Watching closely: A ratiometric fluorescent probe was engineered to detect the clinically relevant platinum drug cisplatin. The ability to distinguish platinum(II) species from their parental platinum(IV) complexes allowed the application of the probe to the study of the activation of platinum(IV) carboxylate prodrug complexes within a complex intracellular environment.