American Chemical Society
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A Flexible Bivalent Approach to Comprehensively Improve the Performances of Stilbazolium Dyes as Amyloid‑β Fluorescent Probes

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journal contribution
posted on 2023-09-18, 18:34 authored by Zi-Min Zhuang, Zhe Zhou, Xian Chen, Xin-Ru Xu, Hang-Xing Wang, Jie Pan
Exploring new ways to reconstruct the structure and function of inappropriate organic fluorophores for improving amyloid-β (Aβ) fluorescent imaging performance is desired for precise detection and early diagnosis of Alzheimer’s disease (AD). With stilbazolium dyes as examples, here, we present a multipronged approach to comprehensively improved the Aβ fluorescent imaging performance through a flexible bivalent method, where a flexible carbon chain was introduced to link two monomers to form a homodimer. Our results reveal a mechanism wherein the flexible linker creates a well-defined probe with specific orientations and distinct photophysical properties. Applying this approach in combination with theoretical simulation, the homodimers exhibited a comprehensive improvement of the Aβ fluorescent imaging performance of the dye monomers, including better photostability and higher signal-to-noise (S/N) ratio, higher “off–on” near-infrared fluorescence (NIRF) response sensitivity, higher specificity and affinity to Aβ deposits, and more reasonable lipophilicity for blood–brain barrier (BBB) penetrability. The results demonstrate that flexible homodimers offer a multipronged approach to obtaining high-performance NIRF imaging reagents for the detection of Aβ deposits both in vitro and in vivo.