意大利巴里大学Giovanni Natile团队报道了¹⁹F-NMR能够用于研究铂(IV)前药物在生理条件下的命运。相关研究成果于2021年11月20日发表在国际顶尖学术期刊《德国应用化学》。

铂（IV）前药可以克服传统铂（II）抗癌疗法的耐药性和副作用。通过对Pt（IV）前药（Pt-FBA，FBA=对氟苯甲酸盐）进行¹⁹F标记，可以研究生理条件下的活化。研究发现，与单电子还原剂不同，多电子还原剂能有效地促进Pt（IV）的双电子还原为Pt（II）。

此外，细胞裂解液中Pt FBA的激活高度依赖于癌细胞的类型。当给予大肠杆菌时，Pt FBA在细胞内减少，游离FBA可以穿梭出细胞。有趣的是，通过诱导金属硫蛋白过度表达，还原率大大增加，而通过添加锌（II）离子，还原率降低。

最后，当注射到小鼠体内时，Pt FBA在血流中迅速减少，伴随着FBA的代谢降解；然而，未减少的Pt FBA可在肝脏和肾脏中累积到可检测的水平。¹⁹F-NMR方法具有避免所有背景信号干扰的优点。

附：英文原文

Title: 19F NMR Allows to Investigate the Fate of Platinum(IV) Prodrugs in Physiological Conditions

Author: Siming Yuan, Yang Zhu, Yi Dai, Yu Wang, Duo Jin, Manman Liu, Liqin Tang, Fabio Arnesano, Yangzhong Liu, Giovanni Natile

Issue&Volume: 2021-11-20

Abstract: Pt(IV) prodrugs can overcome resistance and side effects of conventional Pt(II) anticancer therapies. By  19  F-labeling of a Pt(IV) prodrug (Pt-FBA, FBA =  p  -fluorobenzoate), the activation under physiological conditions could be investigated. It is found that, unlike single-electron reductants, multi-electron agents can efficiently promote the two electrons reduction of Pt(IV) to Pt(II). Moreover, the activation of Pt-FBA in cell lysate is highly dependent upon the type of cancer cells. When administered to  E. coli  , Pt-FBA is reduced intracellularly and free FBA can shuttle out of the cell. Interestingly, the reduction rate greatly increases by inducing metallothionein overexpression and is lowered by addition of Zn(II) ions. Finally, when injected into mice, Pt-FBA undergoes fast reduction in the bloodstream accompanied by metabolic degradation of FBA; nevertheless, unreduced Pt-FBA can accumulate to detectable levels in liver and kidneys. The proposed  19  F-NMR approach has the advantage of avoiding the interference of all background signals.

DOI: 10.1002/anie.202114250

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202114250