Zhou Yongqing, Li Ping, Wang Xin, Wu Chuanchen, Fan Nannan, Liu Xiaoning, Wu Lijie, Zhang Wei, Zhang Wen, Liu Zhenzhen, Tang Bo
College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University Jinan 250014 People's Republic of China
Chem Sci. 2020 Oct 6;11(44):12149-12156. doi: 10.1039/d0sc02922j.
Non-alcoholic fatty liver disease (NAFLD) can gradually develop into hepatic failure, and early diagnosis is crucial to improve treatment efficiency. The occurrence of NAFLD is closely related to lipid metabolism. Peroxisomes act as the first and main site for lipid metabolism in the hepatocytes, so abnormal lipid metabolism might directly affect peroxisomal viscosity. Herein, we developed a new near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging probe (PV-1) for the real-time visualization of peroxisomal viscosity . This PV-1 encompasses the malononitrile group as the rotor, which emits strong NIRF (at 705 nm) and PA (at 680 nm) signals when rotation is hindered as viscosity increases. Through dual-mode imaging, we discovered distinctly higher viscosity in the liver of NAFLD mice for the first time. We further found the remarkable amelioration of NAFLD upon treatment with -acetylcysteine (NAC). Therefore, we anticipate that the PV-1 imaging method is promising for the early diagnosis and prognostic evaluation of NAFLD.
非酒精性脂肪性肝病(NAFLD)可逐渐发展为肝衰竭,早期诊断对于提高治疗效果至关重要。NAFLD的发生与脂质代谢密切相关。过氧化物酶体是肝细胞脂质代谢的首要和主要场所,因此脂质代谢异常可能直接影响过氧化物酶体的黏度。在此,我们开发了一种新型近红外荧光(NIRF)和光声(PA)成像探针(PV-1),用于实时可视化过氧化物酶体黏度。该PV-1包含丙二腈基团作为转子,当黏度增加导致旋转受阻时,会发出强烈的NIRF信号(705nm)和PA信号(680nm)。通过双模态成像,我们首次发现NAFLD小鼠肝脏中的黏度明显更高。我们进一步发现,用N-乙酰半胱氨酸(NAC)治疗后,NAFLD有显著改善。因此,我们预计PV-1成像方法在NAFLD的早期诊断和预后评估方面具有广阔前景。