State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.
Department of Chemistry, University of Bath, Bath, BA2 7AY, UK.
Adv Healthc Mater. 2023 Oct;12(25):e2300733. doi: 10.1002/adhm.202300733. Epub 2023 Aug 27.
β-amyloid (Aβ) is one of the important biomarkers for diagnosing Alzheimer's disease (AD). Many near-infrared probes based on the donor-π-acceptor structure have been developed to detect Aβ. Most reported Aβ probes are based on the N,N-dimethylamino group as the ideal donor, which is a widely accepted binding unit. As such, the development of fluorescent probes with improved binding units to detect Aβ is urgently required. Therefore, with this research three anchoring molecular rotor electron donors consisting of cyclic amines of different ring sizes are developed, namely five-membered ring (TPyr), six-membered ring (TPip), and seven-membered ring (THAI). These new anchored molecular rotors are connected to a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) and named TPyrBDP, TPipBDP, and THAIBDP. These probes exhibit high affinities (from 28 to 54 nm) for Aβ aggregates. The six-membered ring dye TPipBDP exhibits the highest signal-to-noise (75.5-fold) and higher affinity (28.30 ± 5.94 nm). TPipBDP can cross the blood-brain barrier and exhibits higher fluorescence enhancement with APP/PS1 (AD) double transgenic (Tg) mice than with wild-type (WT) mice.
β-淀粉样蛋白 (Aβ) 是诊断阿尔茨海默病 (AD) 的重要生物标志物之一。已经开发出许多基于给体-π-受体结构的近红外探针来检测 Aβ。大多数报道的 Aβ 探针都是基于 N,N-二甲基氨基作为理想的供体，这是一个被广泛接受的结合单元。因此，迫切需要开发具有改进的结合单元的荧光探针来检测 Aβ。因此，本研究开发了三种由不同环大小的环状胺组成的锚定分子转子电子供体，分别为五元环 (TPyr)、六元环 (TPip) 和七元环 (THAI)。这些新的锚定分子转子与 4,4-二氟-4-硼-3a,4a-二氮杂-s-茚 (BODIPY) 相连，分别命名为 TPyrBDP、TPipBDP 和 THAIBDP。这些探针对 Aβ 聚集物表现出高亲和力（从 28 到 54nm）。六元环染料 TPipBDP 表现出最高的信噪比（75.5 倍）和更高的亲和力（28.30 ± 5.94nm）。TPipBDP 可以穿过血脑屏障，并在 APP/PS1 (AD) 双转基因 (Tg) 小鼠中表现出比野生型 (WT) 小鼠更高的荧光增强。
