Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet–Hydrogel Frameworks

The
promising potential of bioorthogonal catalysis in biomedicine
is inspiring incremental efforts to design strategies that regulate
drug activity in living systems. To achieve this, it is not only essential
to develop customized inactive prodrugs and biocompatible metal catalysts
but also the right physical environment for them to interact and enable
drug production under spatial and/or temporal control. Toward this
goal, here, we report the first inactive precursor of the potent broad-spectrum
anticancer drug paclitaxel (a.k.a. Taxol) that is stable in cell culture
and labile to Pd catalysts. This new prodrug is effectively uncaged
in cancer cell culture by Pd nanosheets captured within agarose and
alginate hydrogels, providing a biodegradable catalytic framework
to achieve controlled release of one of the most important chemotherapy
drugs in medical practice. The compatibility of bioorthogonal catalysis
and physical hydrogels opens up new opportunities to administer and
modulate the mobility of transition metal catalysts in living environs.