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Bioluminescent Probe for Tumor Hypoxia Detection via CYP450 Reductase in Living Animals

Author:
Gao, Yuqi, Lin, Yuxing, Liu, Tingting, Chen, Hui, Yang, Xiaofeng, Tian, Chengsen, Du, Lupei, Li, Minyong
Source:
Analytical chemistry 2017 v.89 no.22 pp. 12488-12493
ISSN:
1520-6882
Subject:
NADP (coenzyme), angiogenesis, animals, bioluminescence, enzymes, hypoxia, image analysis, immune system, metastasis, neoplasms, normoxia, therapeutics
Abstract:
Hypoxia is a pathogenic characteristic of solid tumors owing to absent or abnormal vasculature in the tumor microenvironment and essential in tumor progression, angiogenesis, metastasis, invasion and resistance to immune system and therapy. In hypoxic environments, CYP450 enzymes are more efficient than in normoxia. Herein, based on the reductive capacity of CYP450 enzymes/NADPH system, we managed to cage aminoluciferin developing a reaction-based bioluminescent probe as well as an imaging method for the hypoxia detection. Exhibiting enhanced about 3-fold total flux in big (1.2 cm-diameter) tumors, Hypoxia BioLuminescent probe (HBL) can afford potential utility for in cellulo and in vivo hypoxia imaging in tumor model mice.
Agid:
5864066