A Dual-Emissive Phosphorescent Polymeric Probe for Exploring Drug-Induced Liver Injury via Imaging of Peroxynitrite Elevation In Vivo.

Abstract

Drug-induced liver injury (DILI) is a widespread clinical problem. The pathophysiological mechanisms of DILI are complicated, and the traditional diagnostic methods for DILI have their limitations. Owing to its convenient operation, high sensitivity, and high specificity, luminescent sensing and imaging as an indispensable tool in biological research and clinical trials may provide an important means for DILI study. Herein, we report the rational design and preparation of a near-infrared dual-phosphorescent polymeric probe (P-ONOO) for exploring the DILI via specific imaging of peroxynitrite (ONOO-) elevation in vivo, which was one of early markers of DILI and very difficult to be detected due to its short half-life and high reactive activity. With the utilization of P-ONOO, the raised ONOO- was visualized successfully in the drug-treated hepatocytes with a high signal-to-noise ratio via ratiometric and time-resolved photoluminescence imaging. Importantly, the ONOO- boost in the acetaminophen-induced liver injury in real time was verified, and the direct observation of the elevated ONOO- production in ketoconazole-induced liver injury was achieved for the first time. Our findings may contribute to understanding the exact mechanism of ketoconazole-induced hepatotoxicity that is still ambiguous. Notably, this luminescent approach for revealing the liver injury works fast and conveniently.