Near‐Infrared Two‐Photon J‐Aggregation‐Induced Organic Fluorescent Dots with Large Stokes‐Shift for Ratiometric Imaging of Hypochlorous Acid in Living Cells and Brains of AD Mice

Abstract Alzheimer's disease (AD) is characterized by multiple toxicity from various biomarkers, and it is very important to monitor the fluctuation of biomarker level in brain tissues to track its early onset, illness progression, and therapeutic effect. Hypochlorous acid (HOCl) is confirmed to be a reliable biomarker to extend the scope of diagnosis. However, the practical applications of the developed conjugated small molecule fluorescent probes for detecting HOCl are often restricted to a large extent by their low solubility, aggregation‐caused quenching (ACQ), unsatisfactory fluorescence brightness, small Strokes‐shift, and lack of self‐correcting ratiometric emitters. In this study, a J‐aggregation‐induced organic fluorescent dot (PBT dots), is reported which is facilely developed by co‐assembling newly designed organic molecule PBT with polymer DSPE‐PEG, for ClO − imaging in living brain‐derived Endothelial (bEnd.3) cells and brain tissues of AD mice. The developed two‐photon PBT dots show NIR emission at 715 nm, large Stokes‐shift of 245 nm, quick response within 2 s, ratiometric sensing properties, and favorable blood‐brain barrier (BBB) penetrate ability. The results demonstrate that HOCl level is elevated in AD mouse brain, and PBT dot holds promise as an imaging probe to understand and reveal AD pathologies.