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A ZIF-90 nanoplatform loaded with an enzyme-responsive organic small-molecule probe for imaging the hypoxia status of tumor cells.
Nanoscale ( IF 5.8 ) Pub Date : 2020-06-22 , DOI: 10.1039/d0nr02580a Ruifen Zou 1 , Qiuyu Gong , Zhenzhi Shi , Jianping Zheng , Jie Xing , Chuang Liu , Zhenqi Jiang , Aiguo Wu
Nanoscale ( IF 5.8 ) Pub Date : 2020-06-22 , DOI: 10.1039/d0nr02580a Ruifen Zou 1 , Qiuyu Gong , Zhenzhi Shi , Jianping Zheng , Jie Xing , Chuang Liu , Zhenqi Jiang , Aiguo Wu
Affiliation
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Hypoxia is one of the most common and important features occurring across a wide variety of malignancies, which can have adverse effects on the therapeutic outcomes of chemotherapy and radiotherapy. Therefore, the characterization of tumor hypoxia is of great importance in clinical tumor treatment. Herein, we firstly develop a new spectroscopic off–on probe with high sensitivity (detection limit: 5.8 ng mL−1) and good selectivity for fluorescence imaging the hypoxic status of tumor cells via its enzymatic reaction with nitroreductase in vitro and in vivo in the presence of dimethyl sulfoxide (DMSO) as a co-solvent. Inspired by the recent investigations on metal–organic frameworks (MOFs), a dual pH and ATP-responsive ZIF-90 nanoplatform was synthesized, and then PEG was post-modified through a Schiff base reaction. This allows the platform to serve as a carrier to load the hypoxia-responsive probe to investigate its response to enzyme in cells and in mice without using dimethyl sulfoxide as a co-solvent. Consequently, the two probes we synthesized here can successfully respond to nitroreductase for turn-on fluorescence imaging at a cellular level and in tumor-bearing mice. This is the first time that an enzyme-responsive organic small-molecule probe has been mounted on one of the MOFs. Our results open up a promising way for the design and application of both enzyme-responsive probes and MOFs.
中文翻译：
装有酶反应性有机小分子探针的ZIF-90纳米平台，用于成像肿瘤细胞的低氧状态。
缺氧是多种恶性肿瘤中最常见，最重要的特征之一，可能会对化学疗法和放射疗法的治疗结果产生不利影响。因此，表征肿瘤缺氧在临床肿瘤治疗中非常重要。在此，我们首先开发一种新的分光偏上以高灵敏度探测（检测极限：5.8纳克毫升-1）和良好的选择性荧光成像肿瘤细胞的低氧状态通过与硝基还原酶其酶促反应在体外和体内在二甲亚砜（DMSO）作为助溶剂存在下。受近期对金属-有机骨架（MOF）的研究的启发，合成了pH和ATP响应的ZIF-90纳米双平台，然后通过席夫碱反应对PEG进行了后修饰。这使得该平台可以用作加载缺氧反应性探针的载体，以研究其对细胞和小鼠中酶的反应，而无需使用二甲基亚砜作为助溶剂。因此，我们在此处合成的两种探针可以成功地响应硝基还原酶，从而在细胞水平和荷瘤小鼠中启动荧光成像。这是第一次将酶反应性有机小分子探针安装在一个MOF上。我们的结果为酶反应探针和MOF的设计和应用开辟了一种有希望的方式。
更新日期：2020-07-16
中文翻译：
装有酶反应性有机小分子探针的ZIF-90纳米平台，用于成像肿瘤细胞的低氧状态。
缺氧是多种恶性肿瘤中最常见，最重要的特征之一，可能会对化学疗法和放射疗法的治疗结果产生不利影响。因此，表征肿瘤缺氧在临床肿瘤治疗中非常重要。在此，我们首先开发一种新的分光偏上以高灵敏度探测（检测极限：5.8纳克毫升-1）和良好的选择性荧光成像肿瘤细胞的低氧状态通过与硝基还原酶其酶促反应在体外和体内在二甲亚砜（DMSO）作为助溶剂存在下。受近期对金属-有机骨架（MOF）的研究的启发，合成了pH和ATP响应的ZIF-90纳米双平台，然后通过席夫碱反应对PEG进行了后修饰。这使得该平台可以用作加载缺氧反应性探针的载体，以研究其对细胞和小鼠中酶的反应，而无需使用二甲基亚砜作为助溶剂。因此，我们在此处合成的两种探针可以成功地响应硝基还原酶，从而在细胞水平和荷瘤小鼠中启动荧光成像。这是第一次将酶反应性有机小分子探针安装在一个MOF上。我们的结果为酶反应探针和MOF的设计和应用开辟了一种有希望的方式。
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