A dual‐channel fluorescent probe for in situ imaging of mitochondrial superoxide and microenvironmental changes in Cd‐induced hepatorenal dysfunction

Abstract Cadmium (Cd) is an environmental pollutant with high bioaccumulation and multi‐organ toxicity, posing a major threat to human health, especially to the liver and kidneys. Fluorescent probes have shown great potential for disease‐related imaging because of their high sensitivity and specificity. However, most existing probes cannot simultaneously image the liver and kidneys in vivo, which limits their application in hepatorenal disease studies. Increasing evidence suggests that ferroptosis, accompanied by mitochondrial dysfunction and oxidative stress, is involved in Cd‐induced hepatorenal injury. Nevertheless, the dynamic changes in key mitochondrial parameters, including reactive oxygen species, polarity, and viscosity, remain poorly understood. Herein, we developed VPS , a mitochondria‐targeted dual‐NIR fluorescent probe responsive to mitochondrial superoxide (O 2 •− ) and microenvironment‐related viscosity/polarity changes. Based on twisted intramolecular charge transfer and ICT mechanisms, VPS showed high sensitivity, good selectivity, and efficient mitochondrial targeting. VPS was successfully applied to fluorescence imaging in Cd‐exposed living cells, zebrafish, and mice, revealing signal changes in the liver and kidneys consistent with increased oxidative stress and altered mitochondrial microenvironments. VPS also enabled evaluation of the protective effect of N‐acetylcysteine. This probe provides a useful platform for dual‐channel imaging of mitochondrial oxidative stress and microenvironment‐related changes in Cd‐induced hepatorenal injury.