- In-Cell Dual Drug Synthesis by Cancer-Targeting Palladium Catalysts
-
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.
- Clavadetscher, Jessica,Indrigo, Eugenio,Chankeshwara, Sunay V.,Lilienkampf, Annamaria,Bradley, Mark
-
-
Read Online
- Palladium-mediated in situ synthesis of an anticancer agent
-
As a novel prodrug activation strategy Pd(0) nanoparticles, entrapped within a modular polymeric support, were used in cell culture, to synthesise the anticancer agent PP-121 from two non-toxic precursors, thereby inducing cell death in the first example of in situ mediated drug synthesis.
- Indrigo, Eugenio,Clavadetscher, Jessica,Chankeshwara, Sunay V.,Lilienkampf, Annamaria,Bradley, Mark
-
supporting information
p. 14212 - 14214
(2016/12/14)
-
- Kinase antagonists
-
The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tryosine kinase, PI3Kinase and mTOR, or PI3Kinase, mTOR and tryosine kinase.
- -
-
Page/Page column 29; 52
(2008/06/13)
-