Selective detection of copper (II) dynamics in living cells and mice with diverse metabolic dysfunction-associated steatotic liver disease using a turn-on bioluminescent probe

Copper is a vital micronutrient that plays a critical role in regulating ecological balance and human physiology. However, excess of copper can have deleterious effects on human health, potentially causing severe diseases, including genetic disorders, neurodegenerative diseases and cancers. Consequently, the development of sensitive and selective probes for the accurate detection of free copper (II) ions (Cu^{2 +}) is imperative for the early diagnosis of Cu-related diseases. In this study, we have developed a turn-on bioluminescent probe, Luc-Cu, for the detection and imaging of Cu²⁺ in vitro and in vivo. In vitro tests demonstrated that Luc-Cu was capable of selectively detecting Cu²⁺ with a 0.35 μM limit of detection. Moreover, Luc-Cu was successfully employed for imaging Cu²⁺ in living cells and tumor-bearing mice. Notably, Luc-Cu has been utilized for the monitoring of Cu²⁺ variation in the livers of mice across diverse stages of metabolic dysfunction-associated steatotic liver disease (MASLD). The exceptional analytical performance of Luc-Cu suggests its potential as a promising and effective imaging tool for the sensitive diagnosis of Cu²⁺-related diseases with high sensitivity.