Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.
NUS Graduate School of Integrative Sciences and Engineering, Institution, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore.
Angew Chem Int Ed Engl. 2019 Jan 2;58(1):164-167. doi: 10.1002/anie.201810361. Epub 2018 Dec 4.
The Pt prodrug strategy has emerged as an excellent alternative to tackle the problems associated with conventional Pt drug therapy. However, there is a lack of tools to study how this new class of Pt drugs are processed at the cellular level. Herein, we report the first ratiometric probe for cisplatin detection and use it to investigate Pt anticancer complexes in biological systems. The probe was able to distinguish between cisplatin and its Pt derivatives, allowing us to probe the intracellular reduction of Pt prodrug complexes. The correlation between the amount of active Pt species available after intracellular reduction of Pt complexes and their cytotoxicity and the role glutathione plays in the reduction of Pt complexes were investigated.
Pt 前药策略已成为解决与传统 Pt 药物治疗相关问题的绝佳选择。然而，目前缺乏研究新型 Pt 药物在细胞水平上如何被处理的工具。在此，我们报告了首个用于顺铂检测的比率探针，并将其用于研究生物体系中的 Pt 抗癌配合物。该探针能够区分顺铂与其 Pt 衍生物，使我们能够探测 Pt 前药配合物的细胞内还原。研究了细胞内还原 Pt 配合物后可用的活性 Pt 物种的数量与其细胞毒性之间的相关性，以及谷胱甘肽在 Pt 配合物还原中的作用。
