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A Ratiometric Fluorescent Probe for Cisplatin: Investigating the Intracellular Reduction of Platinum(IV) Prodrug Complexes
Author(s) -
Ong Jun Xiang,
Lim Carine Shu Qing,
Le Hai Van,
Ang Wee Han
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201810361
Subject(s) - prodrug , cisplatin , intracellular , chemistry , cytotoxicity , glutathione , combinatorial chemistry , platinum , fluorescence , biophysics , pharmacology , biochemistry , catalysis , in vitro , chemotherapy , enzyme , biology , genetics , physics , quantum mechanics
Abstract The Pt IV prodrug strategy has emerged as an excellent alternative to tackle the problems associated with conventional Pt II drug therapy. However, there is a lack of tools to study how this new class of Pt IV drugs are processed at the cellular level. Herein, we report the first ratiometric probe for cisplatin detection and use it to investigate Pt IV anticancer complexes in biological systems. The probe was able to distinguish between cisplatin and its Pt IV derivatives, allowing us to probe the intracellular reduction of Pt IV prodrug complexes. The correlation between the amount of active Pt II species available after intracellular reduction of Pt IV complexes and their cytotoxicity and the role glutathione plays in the reduction of Pt IV complexes were investigated.