Design, Synthesis, and Performance Characterization of BODIPY-Based NIR Probes for Aβ₄₂ 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 Aβ₄₂ 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 Aβ₄₂ 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 Aβ₄₂ aggregates, which showed good optical properties. Cell imaging experiments showed that BQ-1 could label Aβ₄₂ 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.