Copper dysregulation is increasingly recognized as a critical yet underexplored factor in diabetic complications; however, its monitoring remains challenging due to the lack of biocompatible and reliable analytical tools. To address this gap, we developed a near-infrared fluorescent nanoprobe, termed D-CRP, by encapsulating a hemicyanine-based copper chelator within a DSPE-PEG2000 matrix. This engineered nanoplatform exhibits excellent colloidal stability, high biocompatibility, and a selective "turn-on" fluorescence response to Cu²⁺ through a chelation-enhanced fluorescence mechanism, which was validated by mass spectrometry and density functional theory calculations. D-CRP demonstrates outstanding selectivity for Cu²⁺ over competing metal ions and maintains robust stability under physiological conditions, with a linear fluorescence response across physiologically relevant concentration ranges. The biomedical utility of D-CRP was further established in diabetic mouse models, where it enabled non-invasive imaging of elevated copper levels in both wound tissues and urine. Notably, metformin treatment significantly attenuated these copper elevations, suggesting a previously unappreciated role of this antidiabetic drug in modulating copper homeostasis. With negligible cytotoxicity in vitro and in vivo, D-CRP represents a promising proof-of-concept platform that warrants further validation in larger clinical cohorts before potential diagnostic applications in copper-related pathologies.
Chen et al. (Mon,) studied this question.