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Ultrasensitive Near-Infrared Fluorescence-Enhanced Probe for in Vivo Nitroreductase Imaging
journal contribution
posted on 2015-05-20, 00:00 authored by Yuhao Li, Yun Sun, Jiachang Li, Qianqian Su, Wei Yuan, Yu Dai, Chunmiao Han, Qiuhong Wang, Wei Feng, Fuyou LiNitroreductase
(NTR) can be overexpressed in hypoxic tumors, thus
the selective and efficient detection of NTR is of great importance.
To date, although a few optical methods have been reported for the
detection of NTR in solution, an effective optical probe for NTR monitoring in vivo is still lacking. Therefore, it is necessary to
develop a near-infrared (NIR) fluorescent detection probe for NTR.
In this study, five NIR cyanine dyes with fluorescence reporting structure
decorated with different nitro aromatic groups, Cy7-1–5, have
been designed and explored for possible rapid detection of NTR. Our
experimental results presented that only a para-nitro
benzoate group modified cyanine probe (Cy7-1) could serve as a rapid
NIR fluorescence-enhanced probe for monitoring and bioimaging of NTR.
The structure–function relationship has been revealed by theoretical
study. The linker connecting the detecting and fluorescence reporting
groups and the nitro group position is a key factor for the formation
of hydrogen bonds and spatial structure match, inducing the NTR catalytic
ability enhancement. The in vitro response and mechanism
of the enzyme-catalyzed reduction of Cy7-1 have been investigated
through kinetic optical studies and other methods. The results have
indicated that an electro-withdrawing group induced electron-transfer
process becomes blocked when Cy7-1 is catalytically reduced to Cy7-NH2 by NTR, which is manifested in enhanced fluorescence intensity
during the detection process. Confocal fluorescence imaging of hypoxic
A549 cells has confirmed the NTR detection ability of Cy7-1 at the
cellular level. Importantly, Cy7-1 can detect tumor hypoxia in a murine
hypoxic tumor model, showing a rapid and significant enhancement of
its NIR fluorescence characteristics suitable for fluorescence bioimaging.
This method may potentially be used for tumor hypoxia diagnosis.
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Keywords
fluorescence bioimagingmurine hypoxic tumor modelNTR monitoringability enhancementdetection processNTR detection abilityfluorescence intensityConfocal fluorescence imagingtumor hypoxia diagnosisnitro group positioncyanine probeNIR cyanine dyestumor hypoxiaVivo Nitroreductase ImagingNitroreductase549 cellsNIR fluorescence characteristicsCydetection probehydrogen bondshypoxic tumors
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