3 years ago

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

In-Cell Dual Drug Synthesis by Cancer-Targeting Palladium Catalysts
Annamaria Lilienkampf, Eugenio Indrigo, Sunay V. Chankeshwara, Jessica Clavadetscher, Mark Bradley
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. Targeted catalysts: Biocompatible Pd catalysts were actively targeted to brain cancer cells and, upon internalization, catalyzed the synthesis of two anticancer drugs simultaneously by a Suzuki–Miyaura cross-coupling reaction of two benign components and by the decaging of a protected prodrug, leading to cell death.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201702404

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