De Novo Design of a Robust Fluorescent Probe for Basal HClO Imaging in a Mouse Parkinson’s Disease Model

Abstract

Elevated HClO gets involved in the pathogenesis of Parkinson’s disease (PD). Herein, a novel fluorescent probe NUU-1 was designed and synthesized. Distinct from the general strategies, NUU-1 features two distinct HClO reactive sites, a HClO-specific reaction site and a HClO-nonspecific reactive site, which in turn endows NUU-1 with the “0 + 1 > 1” amplification effect, that thus dramatically promotes the selectivity. NUU-1 displayed a fast response rate (within 15 s), remarkable fluorescence enhancement (about 538-fold), and excellent sensitivity (LOD = 25.8 nM) in response to HClO while the remaining fluorescence silence toward other common ROS (H₂O₂, ^•OH, ONOO^–, O₂^•–, and ¹O₂) even at high concentrations (up to 0.5 mM). NUU-1 allows for the imaging of both exogenous and endogenous HClO in living dopaminergic cells (SH-SY5Y). Moreover, by employing NUU-1 as the probe, the image of HClO in C. elegans and zebrafish was successfully achieved. Significantly, in the first trial, NUU-1 was successfully utilized for the brain basal HClO imaging in PD mice models and distinguished PD brain tissues from normal control, thereby holding great potential for in-depth biological applications.