Ultrasensitive
Near-Infrared Fluorescence-Enhanced
Probe for <i>in Vivo</i> Nitroreductase Imaging
Yuhao Li
Yun Sun
Jiachang Li
Qianqian Su
Wei Yuan
Yu Dai
Chunmiao Han
Qiuhong Wang
Wei Feng
Fuyou Li
10.1021/jacs.5b04097.s001
https://acs.figshare.com/articles/journal_contribution/Ultrasensitive_Near_Infrared_Fluorescence_Enhanced_Probe_for_i_in_Vivo_i_Nitroreductase_Imaging/2165428
Nitroreductase
(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 <i>in vivo</i> 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 <i>para</i>-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 <i>in vitro</i> 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-NH<sub>2</sub> 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.
2015-05-20 00:00:00
fluorescence bioimaging
murine hypoxic tumor model
NTR monitoring
ability enhancement
detection process
NTR detection ability
fluorescence intensity
Confocal fluorescence imaging
tumor hypoxia diagnosis
nitro group position
cyanine probe
NIR cyanine dyes
tumor hypoxia
Vivo Nitroreductase ImagingNitroreductase
549 cells
NIR fluorescence characteristics
Cy
detection probe
hydrogen bonds
hypoxic tumors