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 (Hg²⁺) 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 Hg²⁺ fluctuations in organ damage are crucial but limited due to the lack of noninvasive and deep tissue imaging probes. Herein, a Hg²⁺-triggered targeted and NIR-II fluorescence/photoacoustic (PA) dual-mode molecular probe (NHG-2) was developed for real-time monitoring Hg²⁺ fluctuations in Hg²⁺-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 Hg²⁺ 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 Hg²⁺-induced acute liver and kidney injury, demonstrating excellent detection sensitivity. Furthermore, NHG-2 can be utilized to evaluate the efficacy of N-acetylcysteine (NAC) in Hg²⁺-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 Hg²⁺ but also provides a potential tool for early diagnosis and treatment evaluation and potential pathogenesis study.