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用于肿瘤细胞和组织中硝基还原酶的内质网靶向双光子荧光探针。

Endoplasmic reticulum-targeted two-photon turn-on fluorescent probe for nitroreductase in tumor cells and tissues.

机构信息

Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Materials Science and Engineering, University of Jinan, Jinan, Shandong 250022, PR China.

Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Materials Science and Engineering, University of Jinan, Jinan, Shandong 250022, PR China.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2018 Nov 5;204:770-776. doi: 10.1016/j.saa.2018.05.092. Epub 2018 May 28.

DOI:10.1016/j.saa.2018.05.092
PMID:30007884
Abstract

Hypoxia conditions could increase the activity of intracellular nitroreductase (NTR) and lead to many malignant diseases. Therefore, monitoring the activity of NTR is of great significance to study the related diseases. Organelles play crucial roles in the metabolism of living cells. In these organelles, the endoplasmic reticulum (ER) possesses single membrane structure, and it is the largest organelle in the cell. ER performs the synthesis, processing and modification of proteins and lipid, stabilizing the intracellular Ca concentration and other physiological functions in living cells. Therefore, it is of great significance to develop ER-target probes in living system. Toward this goal, a new endoplasmic reticulum-targeted two-photon fluorescence turn-on NTR probe Na-NTR-ER is designed and synthesized. Probe Na-NTR-ER has been proved to display high sensitivity (36 ng/mL) and selectivity to NTR. Particularly, probe Na-NTR-ER has been successfully applied for the monitoring of NTR in ER with a high the Pearson's colocalization coefficient as 0.90 in HeLa cells and cancerous mouse tissues up to the depth of 100 μm with significant fluorescence signals.

摘要

缺氧条件可能会增加细胞内硝基还原酶 (NTR) 的活性,导致许多恶性疾病。因此,监测 NTR 的活性对于研究相关疾病具有重要意义。细胞器在活细胞的代谢中起着至关重要的作用。在这些细胞器中,内质网 (ER) 具有单层膜结构,是细胞中最大的细胞器。ER 在内质网中进行蛋白质和脂质的合成、加工和修饰,稳定细胞内 Ca 浓度等生理功能。因此,在活体系统中开发内质网靶向探针具有重要意义。为此,设计并合成了一种新的内质网靶向双光子荧光开启 NTR 探针 Na-NTR-ER。实验证明,探针 Na-NTR-ER 对 NTR 具有高灵敏度 (36ng/mL) 和选择性。特别是,探针 Na-NTR-ER 已成功应用于 ER 中 NTR 的监测,在 HeLa 细胞和癌症小鼠组织中的 Pearson 共定位系数高达 0.90,在深度达 100μm 时仍具有显著的荧光信号。

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