TY - JOUR
T1 - Development of a bioluminescent nitroreductase probe for preclinical imaging
AU - Vorobyeva, Anzhelika G.
AU - Stanton, Michael
AU - Godinat, Aurélien
AU - Lund, Kjetil B.
AU - Karateev, Grigory G.
AU - Francis, Kevin P.
AU - Allen, Elizabeth
AU - Gelovani, Juri G.
AU - McCormack, Emmet
AU - Tangney, Mark
AU - Dubikovskaya, Elena A.
N1 - Publisher Copyright:
© 2015 Vorobyeva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/6/25
Y1 - 2015/6/25
N2 - Bacterial nitroreductases (NTRs) have been widely utilized in the development of novel antibiotics, degradation of pollutants, and gene-directed enzyme prodrug therapy (GDEPT) of cancer that reached clinical trials. In case of GDEPT, since NTR is not naturally present in mammalian cells, the prodrug is activated selectively in NTR-transformed cancer cells, allowing high efficiency treatment of tumors. Currently, no bioluminescent probes exist for sensitive, non-invasive imaging of NTR expression. We therefore developed a "NTR caged luciferin" (NCL) probe that is selectively reduced by NTR, producing light proportional to the NTR activity. Here we report successful application of this probe for imaging of NTR in vitro, in bacteria and cancer cells, as well as in vivo in mouse models of bacterial infection and NTR-expressing tumor xenografts. This novel tool should significantly accelerate the development of cancer therapy approaches based on GDEPT and other fields where NTR expression is important.
AB - Bacterial nitroreductases (NTRs) have been widely utilized in the development of novel antibiotics, degradation of pollutants, and gene-directed enzyme prodrug therapy (GDEPT) of cancer that reached clinical trials. In case of GDEPT, since NTR is not naturally present in mammalian cells, the prodrug is activated selectively in NTR-transformed cancer cells, allowing high efficiency treatment of tumors. Currently, no bioluminescent probes exist for sensitive, non-invasive imaging of NTR expression. We therefore developed a "NTR caged luciferin" (NCL) probe that is selectively reduced by NTR, producing light proportional to the NTR activity. Here we report successful application of this probe for imaging of NTR in vitro, in bacteria and cancer cells, as well as in vivo in mouse models of bacterial infection and NTR-expressing tumor xenografts. This novel tool should significantly accelerate the development of cancer therapy approaches based on GDEPT and other fields where NTR expression is important.
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U2 - 10.1371/journal.pone.0131037
DO - 10.1371/journal.pone.0131037
M3 - Article
C2 - 26110789
AN - SCOPUS:84938391974
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e0131037
ER -