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In-Cell Dual Drug Synthesis by Cancer-Targeting Palladium Catalysts

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http://doi.wiley.com/10.1002/anie.201702404
Original languageEnglish
JournalAngewandte Chemie International Edition
Early online date9 May 2017
DOIs
Publication statusE-pub ahead of print - 9 May 2017

Abstract

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.

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