College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, PR China.
College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan, 250014, PR China.
Anal Chim Acta. 2022 May 22;1208:339825. doi: 10.1016/j.aca.2022.339825. Epub 2022 Apr 20.
Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction and peripheral vascular disease, which is an important disease threatening human health. Abnormal levels of protein phosphorylation are closely related to the occurrence and development of diseases. Herein, the ratiometric fluorescence nanosensor (PCN/W- B@BSA) was prepared by using metal-organic frameworks (PCN-224) and fluorescent nanocluster wool-balls, which was applied for ratiometric fluorescence imaging of protein phosphorylation level in the AS mice model. Specific recognition of phosphorylation sites was achieved via specific interaction between active center Zr(IV) and phosphate. Using the two-photon property of porphyrin, the background is significantly reduced, and the sensitivity of imaging analysis is improved by combining with ratio imaging. Bovine serum albumin (BSA) was used to modify the surface of the nanosensor to reduce the non-specific adsorption and improve the biocompatibility of the nanosensor. Finally, the fluorescence nanosensor was successfully apply to fluorescence imaging of protein phosphorylation level in AS mice model, and the results showed that the protein phosphorylation level in the AS mice model was lower than that of the normal mice. The present study provides suitable fluorescence tool for further revealing phosphorylation related signaling pathways and disease mechanisms.
动脉粥样硬化（AS）是冠心病、脑梗死和外周血管疾病的主要病因，是威胁人类健康的重要疾病。蛋白质磷酸化水平的异常与疾病的发生和发展密切相关。本文通过金属有机骨架（PCN-224）和荧光纳米簇毛球制备了比率荧光纳米传感器（PCN/W-B@BSA），用于动脉粥样硬化小鼠模型中蛋白质磷酸化水平的比率荧光成像。通过活性中心 Zr（IV）与磷酸盐之间的特异性相互作用实现对磷酸化位点的特异性识别。利用卟啉的双光子特性，结合比率成像，显著降低了背景，提高了成像分析的灵敏度。牛血清白蛋白（BSA）被用来修饰纳米传感器的表面，以减少非特异性吸附，提高纳米传感器的生物相容性。最后，成功地将荧光纳米传感器应用于动脉粥样硬化小鼠模型中蛋白质磷酸化水平的荧光成像，结果表明，动脉粥样硬化小鼠模型中的蛋白质磷酸化水平低于正常小鼠。本研究为进一步揭示磷酸化相关信号通路和疾病机制提供了合适的荧光工具。
