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

• Published in: Nature chemistry Vol. 7; no. 7; pp. 597 - 603
• Main Authors: Tonga, Gulen Yesilbag, Jeong, Youngdo, Duncan, Bradley, Mizuhara, Tsukasa, Mout, Rubul, Das, Riddha, Kim, Sung Tae, Yeh, Yi-Cheun, Yan, Bo, Hou, Singyuk, Rotello, Vincent M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2015; Nature Publishing Group
• Subjects: 639/638/541; 639/638/77/603; 639/925/352; 639/925/357/354; Analytical Chemistry; Biochemistry; Biomimetics; Catalysis; Chemistry; Chemistry/Food Science; Fabrication; HeLa Cells; Humans; Inorganic Chemistry; Metal Nanoparticles - chemistry; Organic Chemistry; Physical Chemistry; Transition Elements - chemistry
• ISSN: 1755-4330; 1755-4349; 1755-4349
• DOI: 10.1038/nchem.2284

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. Regulation of bioorthogonal catalysis in living systems is challenging because of the complex intracellular environment. Now, the activity of protein-sized bioorthogonal nanozymes has been regulated by binding a supramolecular cucurbit[7]uril ‘gate-keeper’ onto the monolayer surface. This arrangement enables the controlled activation of profluorophores and prodrugs inside living cells for imaging and therapeutic applications.