In-Cell Dual Drug Synthesis by Cancer-Targeting Palladium Catalysts
In-Cell Dual Drug Synthesis by Cancer-Targeting Palladium Catalysts
复制标题
DOI：
10.1002/anie.201702404
复制
发表时间：
2017-06-06
影响因子：
16.6
通讯作者：
Bradley, Mark
中科院分区：
文献类型：
--
作者：
Clavadetscher, Jessica;Indrigo, Eugenio;Bradley, Mark
过渡金属已经成功地应用于催化活细胞内的非天然化学转化，高效标记亚细胞组分和激活前药。然而，在体内的应用，一直是稀缺的，与特定的细胞靶向的活性过渡金属的需要。在这里，我们展示了癌症靶向钯催化剂的设计和应用，其在脑癌（胶质母细胞瘤）细胞中的特异性摄取，同时保持其催化活性。在这些细胞中，首次通过两种完全不同的机制（原位合成和去老化）在细胞内同时合成了两种不同的抗癌剂，增强了药物的治疗效果。催化剂的肿瘤特异性以及它们同时进行多个生物正交转化的能力将使过渡金属在体内用于药物活化策略的应用成为可能。
Transition metals have been successfully applied to catalyze non-natural chemical transformations within living cells, with the highly efficient labeling of subcellular components and the activation of prodrugs. In vivo applications, however, have been scarce, with a need for the specific cellular targeting of the active transition metals. Here, we show the design and application of cancer-targeting palladium catalysts, with their specific uptake in brain cancer (glioblastoma) cells, while maintaining their catalytic activity. In these cells, for the first time, two different anticancer agents were synthesized simultaneously intracellularly, by two totally different mechanisms (in situ synthesis and decaging), enhancing the therapeutic effect of the drugs. Tumor specificity of the catalysts together with their ability to perform simultaneous multiple bioorthogonal transformations will empower the application of in vivo transition metals for drug activation strategies.