A novel NIR fluorescent probe for copper(ii) imaging in Parkinson's disease mouse brain.

Abnormal copper ion (Cu) levels are considered to be one of the pathological factors of Parkinson's disease (PD), but the internal relationship between Cu and PD progression remains elusive. Visualizing Cu in the brain will be pivotal for comprehending the underlying pathophysiological processes of PD. In this work, a near-infrared (NIR) fluorescent probe, DDAO-Cu, capable of detecting Cu with exceptional sensitivity (about 1.8 nM of detection limit) and selectivity, rapid response (<3 min), and deep tissue penetration, was designed for quantification and visualization of the Cu level. It could detect not only Cu in cells but also the changes in the Cu level in the rotenone-induced cell and zebrafish PD models. Moreover, DDAO-Cu can cross the blood-brain barrier to image Cu in the brain of PD model mice. The imaging result showed a significant increase in Cu levels in brain regions of PD model mice, including the cerebral cortex, hippocampus, and striatum. Meanwhile, Cu levels in the substantia nigra region were significantly reduced in PD model mice. It revealed the nuanced relationship of Cu levels in different brain regions in the disease and indicated the pathological complexity of PD. Overall, DDAO-Cu represents a novel and practical tool for investigating Cu-related physiological and pathological processes underlying Parkinson's disease.