A Cofactor-Substrate-Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions.
Yang JiaoLei ZhangXu GaoWen SiChun-Ying DuanPublished in: Angewandte Chemie (International ed. in English) (2020)
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.
Keyphrases
- living cells
- fluorescent probe
- energy transfer
- quantum dots
- early stage
- electron transfer
- structural basis
- amino acid
- water soluble
- poor prognosis
- single molecule
- endothelial cells
- drug delivery
- lymph node
- squamous cell carcinoma
- loop mediated isothermal amplification
- molecular dynamics simulations
- neoadjuvant chemotherapy
- papillary thyroid
- long non coding rna
- cancer therapy
- lymph node metastasis
- real time pcr
- drug induced