posted on 2023-09-18, 18:34authored byZi-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.