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A coelenterazine-type bioluminescent probe for nitroreductase imaging.

Xingye Yang1, Zhenzhen Li, Tianyu Jiang

  • 1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China. mli@sdu.edu.cn.

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|December 9, 2017
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New bioluminescent probes detect nitroreductase (NTR) in hypoxic tumors. Probe A5 demonstrates high sensitivity and compatibility for assessing tumor hypoxia in cells and living organisms.

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Area of Science:

  • Biochemistry
  • Organic Chemistry
  • Molecular Imaging

Background:

  • Hypoxic tumors pose challenges in cancer treatment due to resistance to therapies.
  • Nitroreductase (NTR) is an enzyme often overexpressed in hypoxic tumor environments.
  • Bioluminescent probes offer sensitive detection methods for biological processes.

Purpose of the Study:

  • To design and synthesize novel coelenterazine-type bioluminescent probes for detecting nitroreductase (NTR).
  • To evaluate the probes' sensitivity, selectivity, and applicability for assessing tumor hypoxia.

Main Methods:

  • Chemical synthesis of coelenterazine-type bioluminescent probes.
  • Enzymatic assays to measure probe response to NTR and other biologically relevant substances.
  • In vitro and in vivo studies to assess probe performance in cellulo and in vivo.

Main Results:

  • The designed probes utilize NTR-catalyzed reduction of a nitrobenzyl moiety to release coelenterazine analogues.
  • Probes demonstrated a 3-fold greater response to NTR compared to other substances.
  • Probes A1, A2, and A5 exhibited high selectivity in a dose-dependent manner.
  • Probe A5 showed high sensitivity, low cytotoxicity, and good compatibility.

Conclusions:

  • The developed coelenterazine-type probes are effective for detecting NTR in hypoxic conditions.
  • Probe A5 is a promising tool for assessing tumor hypoxia in both cellular and whole-organism models.
  • This represents the first coelenterazine-type bioluminescent probe successfully applied for in vivo hypoxia assessment.