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In‐Cell Dual Drug Synthesis by Cancer‐Targeting Palladium Catalysts
Author(s) -
Clavadetscher Jessica,
Indrigo Eugenio,
Chankeshwara Sunay V.,
Lilienkampf Annamaria,
Bradley Mark
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201702404
Subject(s) - bioorthogonal chemistry , prodrug , catalysis , in vivo , chemistry , cancer cell , drug , combinatorial chemistry , palladium , cancer , cancer research , nanotechnology , materials science , biochemistry , pharmacology , biology , click chemistry , microbiology and biotechnology , genetics
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.