Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe
Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe
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DOI：
10.1021/acssensors.9b00360
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发表时间：
2019-05-01
期刊：
影响因子：
8.9
通讯作者：
Lippert, Alexander R.
中科院分区：
文献类型：
--
作者：
Ryan, Lucas S.;Gerberich, Jeni;Lippert, Alexander R.
氧合和组织缺氧在哺乳动物生物学中起着关键作用，并有助于癌性肿瘤的侵袭性表型，推动研究开发准确且易于实施的方法来监测活细胞和动物模型中的缺氧。这项研究报告了荧光探针HyCL-4-AM，它含有一个硝基芳香族传感部分，重要的是，乙酰氧基甲基（AM）酯，显着提高在细胞和动物中的操作。HyCL-4-AM在大鼠肝微粒体（RLM）存在下提供了选择性60 000倍的发光增加。对于细胞操作，化学发光响应动力学强烈依赖于氧水平，使得能够高度显著且可再现地测量活细胞中的缺氧。在肌肉组织和肿瘤异种移植物中的全动物成像实验表明，HyCL-4-AM可以区分良好氧合的肌肉组织和缺氧肿瘤，证明了通过高氧治疗监测肿瘤再氧合的潜力。
Oxygenation and tissue hypoxia play critical roles in mammalian biology and contribute to aggressive phenotypes in cancerous tumors, driving research to develop accurate and easy-to-implement methods for monitoring hypoxia in living cells and animal models. This study reports the chemiluminescent probe HyCL-4-AM, which contains a nitroaromatic sensing moiety and, importantly, an acetoxymethyl (AM) ester that dramatically improves operation in cells and animals. HyCL-4-AM provides a selective 60 000-fold increase in luminescence emission in the presence of rat liver microsomes (RLM). For cellular operation, the chemiluminescence response kinetics is sharply dependent on oxygen levels, enabling highly significant and reproducible measurement of hypoxia in living cells. Whole animal imaging experiments in muscle tissue and tumor xenografts show that HyCL-4-AM can differentiate between well oxygenated muscle tissue and hypoxic tumors, demonstrating potential for monitoring tumor reoxygenation via hyperoxic treatment.