TY - JOUR
T1 - A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells
AU - Kumari, Rashmi
AU - R, Vasumathy
AU - Sunil, Dhanya
AU - Ningthoujam, Raghumani Singh
AU - Pandey, Badri Narain
AU - Kulkarni, Suresh D.
AU - Varadavenkatesan, Thivaharan
AU - Venkatachalam, Ganesh
AU - V, Anil Kumar N.
N1 - Funding Information:
This work is a part of the PhD thesis of RK. DS and AKNV acknowledge the financial support by Department of Atomic Energy (DAE), Board of Research in Nuclear Sciences (BRNS) with sanction number 37(2)/14/01/2018-BRNS/37001. CECRI Manuscript Communication Number: CECRI/PESVC/Pubs./2021-105.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/11
Y1 - 2021/11
N2 - The bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4−nitro−1,8−naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR−aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF−7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions. Graphical abstract: [Figure not available: see fulltext.]
AB - The bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4−nitro−1,8−naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR−aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF−7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions. Graphical abstract: [Figure not available: see fulltext.]
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U2 - 10.1007/s10895-021-02800-6
DO - 10.1007/s10895-021-02800-6
M3 - Article
AN - SCOPUS:85112392467
SN - 1053-0509
VL - 31
SP - 1665
EP - 1673
JO - Journal of Fluorescence
JF - Journal of Fluorescence
IS - 6
ER -
