Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 15, Pages 6021-6027Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201915040
Keywords
cofactor mimics; enzymes; hypoxia; metal-organic capsules; supramolecular chemistry
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Funding
- NSFC [21977015, 21820102001, 21531001]
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Identifying the location and expression levels of enzymes under hypoxic conditions in cancer cells is vital in early-stage cancer diagnosis and monitoring. By encapsulating a fluorescent substrate, L-NO2, within the NADH mimic-containing metal-organic capsule Zn-MPB, we developed a cofactor-substrate-based supramolecular luminescent probe for ultrafast detection of hypoxia-related enzymes in solution in vitro and in vivo. The host-guest structure fuses the coenzyme and substrate into one supramolecular probe to avoid control by NADH, switching the catalytic process of nitroreductase from a double-substrate mechanism to a single-substrate one. This probe promotes enzyme efficiency by altering the substrate catalytic process and enhances the electron transfer efficiency through an intra-molecular pathway with increased activity. The enzyme content and fluorescence intensity showed a linear relationship and equilibrium was obtained in seconds, showing potential for early tumor diagnosis, biomimetic catalysis, and prodrug activation.
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