Palladium-Sensitive Chemicals and Engineered Pd(0)-Containing Devices to Implement Highly-Specific Probe/Prodrug Activation in Cells and Living Systems

As a novel prodrug / probe approach, our group is pioneering the use of a bioorthogonal organometallic (BOOM) activation strategy to develop spatially-controlled anticancer treatments. Bioorthogonal reactions are selective chemical processes that take place in biological systems, mediated by abiotic reagents, without interfering with the biotic components of the system [1, 2]. The use of bioorthogonal protecting groups that are selectively cleaved by metal catalysis allows to chemically “mask” the functional properties of a drug / fluorescent dye to induce local activation by a catalyst-based “activating device”. We are currently investigating the use of Pd0-containing implants (the “activating device”) and the chemical modification of clinically-used anticancer drugs with Pd0-sensitive chemical groups to make “BOOM-activated prodrugs”. In this talk the seminal works published in this area [2, 3] and our last results will be presented.

References:
[1] Prescher&Bertozzi. Nature Chem Biol 2005, 1, 13–21; [2] Unciti-Broceta et al. Nature Protocols 2012, 7, 1207–18; [3] Yusop, Unciti-Broceta et al. Nature Chem 2011, 3, 241–245.