Viscosity-responsive signal amplification dual-modal probe triggered by cysteine/homocysteine for monitoring diabetic liver damages and repair processes

Diabetic liver injury is a widespread complication of diabetes and carries a high risk to liver function. Therefore, early diagnosis of diabetic liver injury is of great significance for providing quality of life for diabetic patients. Most of the activated dual-modal probes are usually activated by single factor stimulation, which greatly reduces the diagnostic accuracy of liver injury. Here, a novel cysteine (Cys)/homocysteine (Hcy) and viscosity-enhanced dual-modal probe DAL was developed for the first time to monitor diabetic liver injury and its repair process. In the presence of Cys/Hcy, the near-infrared fluorescence (NIRF) and photoacoustic (PA) signals of the probe DAL were activated, with further signal enhancement in high viscosity environments. This Cys/Hcy and viscosity cascade probe exhibits heightened sensitivity and enhanced anti-interference capabilities, contributing to the advancement of liver injury diagnosis accuracy. In addition, the probe DAL shows exceptional mitochondrial targeting ability, enabling sensitive monitoring of Cys/Hcy and viscosity alterations within mitochondria. Based on NIRF/PA dual-modal imaging technology, the probe was successfully used for the first time in a mouse diabetic liver injury model to evaluate the extent of liver damage and the repair process by tracking the levels of Cys/Hcy and viscosity. Therefore, the two-factor activated dual-modal probe developed in this study provides a powerful instrument for accurate diagnosis and efficacy evaluation of complications related to diabetes.