Journal of Materials Chemistry B
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2019
·Vol. 7
·期 43
·6822-6827
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IF 5.047
Fanpeng Kong,Ying Li,Chao Yang,Xiao Li,Junlin Wu,Xiaojun Liu,Xiaonan Gao,Kehua Xu,Bo Tang
Identifying cancer at the cellular level during an early stage offers the hope of greatly improved outcomes for cancer patients. As potential cancer biomarkers, nitroreductase (NTR) and human quinine oxidoreductase 1 (hNQO1) are overexpressed in many type of cancer cells. Simultaneous detection of these two biomarkers would benefit diagnostic precision in related cancers without yielding false positive results. Herein, based on a dye generated in situ strategy, a dual-enzyme-responsive probe, CNN, was rationally designed and synthesized by installing p-nitrobenzene and trimethyl-locked quinone propionic acid groups, which are specific for NTR and hNQO1, respectively, into a single fluorophore. This probe is only activated in the presence of both NTR and hNQO1 and produces a large fluorescence response, enabling the detection of both endogenous NTR and hNQO1 activity in living cells. The imaging results indicate that the CNN probe differentiates cancer cells (HeLa, MDA-MB-231 and HepG2 cells) from normal liver HL-7702 cells owing to the existence of relatively high endogenous levels of both biomarkers in these cancer cells.
研究领域:
癌症生物学
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生物化学
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分子生物学
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细胞生物学
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生物医学工程
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2022
·
IF 4.831
Xianghan Zhang,Zhiqing Gao,Yuqiong Xia,Qunyan Dong,Yutian Cao,Qian Jia,Fang Sun,Zheng Li,Chu Tang,Jie Yu
Nitroreductase (NTR) detection in tumor is critical because NTR level is correlated with hypoxia degree and cancer prognosis. With the feature of high sensitivity and selectivity, fluorescence organic probes for NTR detection exhibited a promising future for tumor hypoxia detection. However, the discovery and design of such probes have been impeded due to the lack of the understanding of spatial match and mismatch of these probes with NTR. Here, we have developed two new nitrophenyl-functionalized trimethincyanine (Cy3) probes with para- or meta- positions of nitro-group in phenyl ring. Para-nitrophenyl substituted Cy3 (pNP-Cy3) exhibited a remarkable response to NTR (20-fold fluorescence enhancement) with good selectivity and sensitivity. Experimental and theoretical analysis verified that the substituent position of nitro group on phenyl ring of dyes altered the spatial arrangement of nitro-substituent group, thereby modulated the spatial match and mismatch between Cy3 dyes and binding domain of NTR, and consequently led to a different fluorescent turn-on response. In tumor-bearing mice model, hypoxia status of A549 xenografted tumor of mice was successfully delineated by using pNP-Cy3. These results may provide a clue for designing new cyanine-derived NTR probe to monitor NTR-overexpressed hypoxia cancer cells.
研究领域:
生物化学
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癌症生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Biomolecules
·
2021
·Vol. 11
·期 9
·1370
·
IF 4.879
Shuyi Liao,Wenmin Yang,Ting Yu,Lu Dai,Xiaoliang Liu,Jiangping Zhang,Jinghong Zhao,Chi Liu
Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed aTg(cdh17:Dendra2-NTR)transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.Keywords:acute renal failure (ARF);cardiorenal syndrome (CRS);zebrafish model;drug screening;nitroreductase (NTR);metronidazole (MTZ)
研究领域:
药理学
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肾脏生理学
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心脏病学
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发育生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）