State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No.163 Xianlin Road, Nanjing, 210023, China.
Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu province hospital, Nanjing, 210029, China.
Mikrochim Acta. 2024 Mar 23;191(4):217. doi: 10.1007/s00604-024-06291-7.
Hypoxia, a significant feature of the tumor microenvironment, is closely associated with tumor growth, metastasis, and drug resistance. In the field of tumor microenvironment analysis, accurately imaging and quantifying hypoxia - a critical factor associated with tumor progression, metastasis, and resistance to therapy - remains a significant challenge. Herein, a hypoxia-activated red-emission fluorescent probe, ODP, for in vivo imaging of hypoxia in the tumor microenvironment is presented. Among various imaging methods, optical imaging is particularly convenient due to its rapid response and high sensitivity. The ODP probe specifically targets nitroreductase (AzoR), an enzyme highly expressed in hypoxic cells, playing a vital role by catalyzing the cleavage of azo bonds. The optical properties of ODP exhibited excellent performance in terms of fluorescence enhancement, fluorescence lifetime (0.81 ns), and detection limit (0.86 µM) in response to SDT. Cell imaging experiments showed that ODP could effectively detect and image intracellular hypoxia and the imaging capability of ODP was studied under various conditions including cell migration, antioxidant treatment, and different incubation times. Through comprehensive in vitro and in vivo experiments, including cellular imaging and mouse tumor models, this work demonstrates the efficacy of ODP in accurately detecting and imaging hypoxia. Moreover, ODP's potential in inducing apoptosis in cancer cells offers a promising avenue for integrating diagnostic and therapeutic strategies in cancer treatment. This innovative approach not only contributes to the understanding and assessment of tumor hypoxia but also opens new possibilities for targeted cancer therapy.
缺氧是肿瘤微环境的一个显著特征，与肿瘤生长、转移和耐药性密切相关。在肿瘤微环境分析领域，准确地对与肿瘤进展、转移和治疗耐药性密切相关的缺氧进行成像和定量仍然是一个重大挑战。在这里，我们提出了一种用于肿瘤微环境中缺氧的近红外二区荧光探针 ODP。在各种成像方法中，由于其快速响应和高灵敏度，光学成像特别方便。ODP 探针特异性靶向硝基还原酶（AzoR），AzoR 是一种在缺氧细胞中高度表达的酶，通过催化偶氮键的裂解，在缺氧环境中发挥着至关重要的作用。ODP 的光学性质在 SDT 响应下表现出优异的荧光增强、荧光寿命（0.81 ns）和检测限（0.86 μM）性能。细胞成像实验表明，ODP 可以有效地检测和成像细胞内缺氧，并且研究了 ODP 在细胞迁移、抗氧化处理和不同孵育时间等各种条件下的成像能力。通过包括细胞成像和小鼠肿瘤模型在内的综合体外和体内实验，该工作证明了 ODP 准确检测和成像缺氧的功效。此外，ODP 在诱导癌细胞凋亡方面的潜力为整合癌症治疗中的诊断和治疗策略提供了一种有前途的方法。这种创新方法不仅有助于理解和评估肿瘤缺氧，而且为靶向癌症治疗开辟了新的可能性。
