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Near-infrared off-on fluorescence probe activated by NTR for in vivo hypoxia imaging. | LitMetric
Selective and efficient detection and imaging of nitroreductase (NTR) overexpressed in hypoxic tissues is of great importance for better understanding its biological functions. The effective optical probes equipped for NTR detection in vivo is still lacking, so we developed an innovative near infrared (NIR) fluorescent on-off probe (Cy-NO) composed of fluorescence reporting unit (an aminocyaine dye) and recognition unit (p-nitrobenzylcarbamate group). The response and mechanism of the NTR activated reduction of Cy-NO were evaluated in vitro through kinetic optical studies, mass spectra analysis and docking calculations. The results demonstrated that Cy-NO could rapidly recognize NTR with high selectivity and sensitivity. The efficient NTR detection ability of Cy7-NO was further validated by fluorescence imaging of hypoxic cells (A549, PC-12 and HUVEC cell). Furthermore, the in vivo hypoxia imaging by Cy-NO were evaluated on tumor-bearing mouse, cerebral ischemia (CIS) and deep vein thrombosis models. The results indicated a rapid and distinct enhancement of its NIR fluorescence highly appropriate for in vivomonitoring of NTR in all of the three animal models, which revealed aspiring clinical value of this NIR fluorescent hypoxia probe.
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