Design, Synthesis, and Performance Characterization of BODIPY‐Based NIR Probes for Aβ ₄₂ Aggregate Detection

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with typical pathological features including β‐amyloid (Aβ) plaques. Achieving early and accurate detection of cerebral Aβ aggregates is essential for timely intervention in AD, but the process is challenging. To address the lack of high‐sensitivity and high signal‐to‐noise ratio near‐infrared imaging tools for the early pathological detection of Aβ, we designed and synthesized two BODIPY‐quinoline‐based fluorescent probes, BQ‐1 and BQ‐2 , for targeting Aβ ₄₂ aggregates. BQ‐1 showed high affinity ( K _D  = 48.81 nM), high sensitivity (LOD = 52 nM), and high signal‐to‐noise ratio (189.5‐fold) for Aβ ₄₂ aggregates. Based on the twisted intramolecular charge transfer (TICT) mechanism, BQ‐1 showed near‐infrared fluorescence emission ( λ _ex / λ _em  = 612/669 nm, Stokes shift 57 nm) after binding to Aβ ₄₂ aggregates, which showed good optical properties. Cell imaging experiments showed that BQ‐1 could label Aβ ₄₂ aggregates in PC12 cells with high selectivity and low cytotoxicity. This study demonstrates that BQ‐1 is a near‐infrared (NIR) fluorescent probe with excellent performance and provides a potential tool for early pathological imaging diagnosis of AD.