Multifunctional lysosome-targetable fluorescent probe for imaging peroxynitrite in acute liver injury model

Abstract

Liver injury is usually caused by different sources (such as drugs, food, and alcohol), which is regarded as a serious threat to human health. Since the current indicators are not well defined, it is crucial to develop novel probes to characterize the kinetic process of liver injury. In this paper, a novel probe with fluorescence signals, Lyso-ONOO, was synthesized to detect the fluctuating peroxynitrite (ONOO−) level in various acute injury model mice. With the addition of ONOO−, the fluorescence response of Lyso-ONOO exhibited a large Stokes shift of 105 nm under 450 nm excitation. The reaction had the merits of high sensitivity, high selectivity, rapid reaction, and stability under various pH conditions. In addition, Lyso-ONOO had prominent lysosome-targeting ability. It achieved monitoring the exogenous and endogenous ONOO− in human hepatic stellate cells. Further, Lyso-ONOO could display endogenous ONOO− in models of 4T1-xenograft and inflammation in mice. More importantly, Lyso-ONOO could gauge the changing levels of ONOO− in three types (induced by CCl4, APAP, and alcohol) of acute liver injury models and treatments (silybin and bicyclol) of CCl4-induced liver injury mice. Both in vivo imaging and depth-of-penetration fluorescence imaging demonstrated that Lyso-ONOO could characterize the developmental and therapeutic status during the liver injury process by measuring the dynamic change of ONOO−. The monitoring of Lyso-ONOO appeared to be useful in inferring the order of severity in diverse acute liver injury processes and taking into account the efficacy of treatment regimens, which might provide important information for corresponding research.