The instability of catalysts in the complex environment within cells hampers the generation of intracellular molecules for imaging and therapeutic applications. Within this context, Vincent Rotello and colleagues now report supramolecular nanoparticles for the gated control of intracellular catalytic activity. The researchers encapsulated transition metal catalysts within the surface layer of polymer-functionalized gold nanoparticles, and used cucurbituril as a supramolecular surface coating to sterically inhibit catalytic turnover. Once endocytosed, the nanoparticles remain inert in cells until an adamantyl guest is added to trigger macrocycle displacement, exposing the catalytic metals. In the presence of an exogenous fluorophore precursor, the activated nanoparticles are able to catalytically produce a fluorescent measure of the intracellular catalytic reaction. They are also able to trigger cell death through the catalytic activation of a synthetic prodrug. This system may inspire further developments for the study and control of dysfunctional cells.
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Hennessy, J. Bioorthogonal catalysts. Nature Mater 14, 750 (2015). https://doi.org/10.1038/nmat4380