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Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts

Abstract

Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril ‘gate-keeper’ onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.

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Figure 1: Bioorthogonal nanozyme design and supramolecular regulation of intracellular catalysis.
Figure 2: Catalytic activity of nanozymes in solution.
Figure 3: Lineweaver–Burk plot showing competitive binding of CB[7] to nanozyme.
Figure 4: Triggered allylcarbamate cleavage in living cells using gated nanozymes.
Figure 5: Prodrug activation in living cells using supramolecularly controlled nanozymes.

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Acknowledgements

This work was supported by a grant from the National Institutes of Health (EB014277). T.M. acknowledges the Japan Society for the Promotion of Sciences for a Postdoctoral Fellowship for Research Abroad and for the Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation. The authors thank L. Isaacs (University of Maryland) for providing cucurbit[7]uril.

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Authors

Contributions

G.Y.T., Y.J. and V.M.R. conceived and designed the experiments. G.Y.T., Y.J., B.D., T.M., R.M., R.D., S.T.K., Y-C.Y., B.Y. and S.H. performed the experiments. All authors analysed and discussed the data. G.Y.T., Y.J., B.D. and V.M.R. co-wrote the paper. V.M.R. revised the paper. G.Y.T. and Y.J. contributed equally to this work.

Corresponding author

Correspondence to Vincent M. Rotello.

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The authors declare no competing financial interests.

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Tonga, G., Jeong, Y., Duncan, B. et al. Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts. Nature Chem 7, 597–603 (2015). https://doi.org/10.1038/nchem.2284

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