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Cited by 516

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Ultrasensitive Near-Infrared Fluorescence-Enhanced Probe for in Vivo Nitroreductase Imaging

Li, Yuhao, Sun, Yun, Li, Jiachang, Su, Qianqian, Yuan, Wei, Dai, Yu, Han, Chunmiao, Wang, Qiuhong, Feng, Wei, Li, Fuyou·2015·Journal of the American Chemical Society

Abstract

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 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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Crossref · 10.1021/jacs.5b04097

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Metadata

Authors
Li, Y., Sun, Y., Li, J., Su, Q., Yuan, W., Dai, Y., Han, C., Wang, Q., Feng, W., & Li, F.
Venue
Journal of the American Chemical Society
Published
2015-05-07
Volume
137
Issue
19
Pages
6407-6416
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
OpenAlex
W2009465544
Cited by
516
References
38
FWCI
19.67
Type
journal article
Language
en
Open access
closed

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