Mercury(II)-Triggered Targeted and NIR-II Fluorescence/Photoacoustic Imaging Probe for High-Sensitivity Early Diagnosis and Evaluating Drug against Acute Liver and Kidney Injury.

Mercury ions (Hg) have been found to disrupt the body's antioxidant defense mechanisms, leading to oxidative stress and physiological dysfunction. Early diagnosis and real-time monitoring of Hg fluctuations in organ damage are crucial but limited due to the lack of noninvasive and deep tissue imaging probes. Herein, a Hg-triggered targeted and NIR-II fluorescence/photoacoustic (PA) dual-mode molecular probe (NHG-2) was developed for real-time monitoring Hg fluctuations in Hg-induced acute liver and kidney injury mice. NHG-2 was designed through rational adjustment of the conjugated ring structure and further screening processes, enabling it to sensitively recognize Hg and subsequently open mitochondrial targeting, producing NIR-II fluorescence/PA signals. This probe allowed for noninvasive NIR-II fluorescence/PA imaging for real-time monitoring of Hg-induced acute liver and kidney injury, demonstrating excellent detection sensitivity. Furthermore, NHG-2 can be utilized to evaluate the efficacy of -acetylcysteine (NAC) in Hg-induced liver and kidney injury through dual signal indication. Mechanism studies suggested that NAC activated the antioxidant Akt/Nrf2 signaling pathway, reversed the changes of related biomarkers, and restored mitochondrial membrane potential. Thus, this study not only presents the first specific NIR-II fluorescence/PA dual-mode probe for Hg but also provides a potential tool for early diagnosis and treatment evaluation and potential pathogenesis study.