A dual-modality sensor for pre-clicinal imaging of diabetes-associated copper dysregulation in vivo and in urine

Copper ions (Cu²⁺) play a critical role in physiological and pathological processes, including diabetes. However, detecting Cu²⁺ with high sensitivity and specificity in diabetes remains challenging. In this study, we developed a hemicyanine-based copper ion probe (CUP) encapsulated in mPEG-DSPE nanoparticles (CUNP) for dual-modality fluorescence and photoacoustic (PA) imaging of Cu²⁺. CUNP exhibited excellent aqueous solubility, biocompatibility, and a turn-on response to Cu²⁺, with activate signals. In vivo studies in streptozotocin (STZ)-induced diabetic mice revealed elevated hepatic Cu²⁺ levels, which were attenuated by metformin treatment, as confirmed by PA and fluorescence imaging. Urine analysis further revealed elevated Cu²⁺ in diabetic patients. These findings highlight CUNP as a promising tool for non-invasive Cu²⁺ monitoring in diabetes, with potential clinical applications in disease diagnosis and therapeutic evaluation.