Guangdong Provincial Key Laboratory of Optical Fiber Sensing and Communication, Institute of Photonics Technology, Jinan University, Guangzhou 511443, China.
Clinical Pharmacology Section, Department of Pharmacology, Shantou University Medical College, Shantou 515041, China.
Analyst. 2022 Mar 28;147(7):1449-1456. doi: 10.1039/d1an01724a.
Detecting nitroreductase (NTR) activity in hypoxic cells and tissues represents an important step toward accurate delineation of hypoxic disease loci. However, it remains challenging to develop fluorescent probes with the necessary attributes of selectivity, sensitivity, precise targeting and aqueous solubility. Herein, two kinds of fluorescent probes (NNP and cRGD-NNP) built on a 2-nitroimidazole sensing platform were synthesized for the detection of NTR activity in cell and models of hypoxia. In the presence of NADH, NNP displayed high selectivity for NTR, a strong fluorescence enhancement (108 fold), and a low detection limit (3.6 ng mL). Benefiting from the hydrophilic structure and tumor-targeting properties of the cRGD cyclopeptide group, the probe cRGD-NNP efficiently detected NTR activity in MCF cancer cells under hypoxia. In addition, the liposome-encapsulated probe was successfully applied to visualize NTR during liver inflammation in mice.
检测缺氧细胞和组织中的硝基还原酶（NTR）活性是准确描绘缺氧疾病部位的重要步骤。然而，开发具有选择性、灵敏度、精确靶向和水溶 性等必要属性的荧光探针仍然具有挑战性。本文基于 2-硝基咪唑感测平台合成了两种荧光探针（NNP 和 cRGD-NNP），用于检测缺氧细胞和模型中的 NTR 活性。在 NADH 的存在下，NNP 对 NTR 表现出高选择性，荧光强度显著增强（108 倍），检测限低（3.6ng/mL）。得益于环肽 cRGD 的亲水性结构和肿瘤靶向特性，探针 cRGD-NNP 能够在缺氧条件下有效检测 MCF 癌细胞中的 NTR 活性。此外，包载于脂质体中的探针成功应用于在体可视化小鼠肝脏炎症中的 NTR。
