In Situ Visualization of Tumor and Drug-Induced Liver Injury with AIEgens, Polarity-Responsive, Membrane-Targeting Fluorescent Probes

Abstract Dynamic changes in the polarity of the cellular microenvironment play a pivotal role in drug-induced liver injury (DILI) and tumors, serving as a crucial biomarker for evaluating cell membrane integrity and functional status. Precise monitoring of polarity changes is essential for elucidating the underlying mechanisms of injury. However, the real-time and specific visualization of local polarity remains a considerable challenge. Herein, polarity-sensitive fluorescent probes Probemem-1 and Probemem-2 were successfully developed. The structures adopted a D-π-A configuration, where a triphenylamine unit served as the electron donor, 1,3-indanedione acted as the electron acceptor, and the two were linked via a thiophene or dithiophene bridge. The triphenylamine moiety endowed Probemem-1 and Probemem-2 with unique aggregation-induced emission (AIE) properties. The fluorescence lifetimes of Probemem-1 and Probemem-2 were markedly prolonged in low-polarity media, demonstrating their pronounced sensitivity to environmental polarity. Importantly, Probemem-2 exhibited better photostability compared to Probemem-1. Analysis of the DILI mouse models revealed a significant correlation between decreased liver polarity and aggravated injury, indicating the potential of polarity as a biomarker for assessing DILI severity. Probemem-1 and Probemem-2 served as efficient molecular tools to track polarity changes, which could facilitate the mechanistic exploration of liver injury.