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A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells |
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| Authors: | Kumari Rashmi R Vasumathy Sunil Dhanya Ningthoujam Raghumani Singh Pandey Badri Narain Kulkarni Suresh D. Varadavenkatesan Thivaharan Venkatachalam Ganesh V Anil Kumar N. |
| Affiliation: | 1.Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India ;2.Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, 400085, Maharashtra, India ;3.Chemistry Division, Bhabha Atomic Research Centre, Mumbai, 400085, Maharashtra, India ;4.Department of Atomic and Molecular Physics, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India ;5.Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India ;6.Electrodics and Electrocatalysis (EEC) Division, CSIR – Central Electrochemical Research Institute (CSIR-CECRI), Karaikudi, 630003, Tamil Nadu, India ;7.Homi Bhabha National Institute, Anushakti Nagar, Mumbai, 400094, India ; |
| Abstract: | 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 |
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