γ-Glutamyltranspeptidase (GGT)-Activatable Fluorescence Probe for Durable Tumor Imaging.
Rui ObaraMako KamiyaYoko TanakaAtsuki AbeRyosuke KojimaTokuichi KawaguchiMinoru SugawaraAkiko TakahashiTetsuo NodaYasuteru UranoPublished in: Angewandte Chemie (International ed. in English) (2020)
γ-Glutamyltranspeptidase (GGT) is overexpressed in several types of cancer. Existing GGT-targeting fluorescence probes can image these cancers, but the fluorescent hydrolysis product leaks from the target cancer cells during prolonged incubation or fixation. Here, we present a functionalized fluorescence probe for GGT, 4-CH2 F-HMDiEtR-gGlu, which is designed to generate an azaquinone methide intermediate during activation by GGT; this intermediate reacts with intracellular nucleophiles to generate a fluorescent adduct that is trapped inside the cells, without loss of the target enzyme activity. Application of the probe to patient-derived xenograft (PDX) mice enabled in vivo cancer imaging for a prolonged period and was also compatible with fixation and immunostaining of the cancer tissue.
Keyphrases
- living cells
- quantum dots
- papillary thyroid
- single molecule
- fluorescent probe
- squamous cell
- high resolution
- energy transfer
- induced apoptosis
- lymph node metastasis
- deep learning
- type diabetes
- squamous cell carcinoma
- metabolic syndrome
- cancer therapy
- signaling pathway
- young adults
- anaerobic digestion
- cell cycle arrest