Department of Chemistry, Organic Chemistry Section, Jadavpur University, Kolkata 700032, India.
J Mater Chem B. 2024 Nov 13;12(44):11368-11380. doi: 10.1039/d4tb01337a.
A striking issue is the scarcity of imaging probes for the early diagnosis of Alzheimer's disease. For the development of Aβ biomarkers, a mitochondria targeting, designed, aggregation-induced emission (AIE) probe Cou-AIE-TPP is constructed by engineering the aromatic coumarin framework into the bridge of electron donor-acceptor-donor tethered with a lipophilic cationic triphenylphosphonium (TPP) group. The synthesized Cou-AIE-TPP probe exhibits biocompatibility, noncytotoxicity, and a huge Stokes shift (124 nm in PBS). Cou-AIE-TPP has respectable fluorescence augmentation inside the aggregated Aβ40 in comparison with monomeric Aβ40 with a high binding affinity ( = 83 nM) to Aβ40 aggregates, is capable of detecting the kinetics of amyloid aggregation, and is superior to the gold standard probe thioflavin T. Fluorescence lifetime and brightness are also augmented when the probe Cou-AIE-TPP binds with Aβ aggregates in PBS. Cou-AIE-TPP ( 604 nm) selectively targets and images neuronal cell mitochondria, is useful to monitor mitochondrial morphology alteration and damage during Aβ40-induced neurotoxicity, recognizes neurotoxic Aβ fibrils, and is highly colocalized with thioflavin T, showing a decent Pearson correlation coefficient of 0.91 in the human neuroblastoma SH-SY5Y cell line. These findings indicate that the mitochondria targeting, designed, functional AIE-based solvatofluorochromic Cou-AIE-TPP probe is a promising switch on biomarkers for fluorescence imaging of Aβ aggregates and to monitor mitochondrial morphology change and dysfunction during Aβ-induced neurotoxicity, which may offer imperative direction for the advancement of compelling AIE biomarkers for targeted early stage Aβ diagnosis in the future.
一个突出的问题是缺乏用于阿尔茨海默病早期诊断的成像探针。为了开发 Aβ 生物标志物，通过将芳香香豆素骨架工程化为带有疏水性阳离子三苯基膦（TPP）基团的电子给体-受体-给体桥，构建了一种靶向线粒体的设计的聚集诱导发射（AIE）探针 Cou-AIE-TPP。合成的 Cou-AIE-TPP 探针具有生物相容性、非细胞毒性和巨大的斯托克斯位移（在 PBS 中为 124nm）。与单体 Aβ40 相比，Cou-AIE-TPP 在聚集的 Aβ40 中具有可观的荧光增强，与 Aβ40 聚集物具有高结合亲和力（=83 nM），能够检测淀粉样蛋白聚集的动力学，并且优于金标准探针硫黄素 T。当探针 Cou-AIE-TPP 在 PBS 中与 Aβ 聚集物结合时，荧光寿命和亮度也会增强。Cou-AIE-TPP（604nm）选择性地靶向和成像神经元细胞线粒体，可用于监测 Aβ40 诱导的神经毒性过程中线粒体形态的改变和损伤，识别神经毒性的 Aβ 原纤维，并且与硫黄素 T 高度共定位，在人神经母细胞瘤 SH-SY5Y 细胞系中显示出相当高的 Pearson 相关系数为 0.91。这些发现表明，这种靶向线粒体的、设计的、基于功能 AIE 的溶剂致变色 Cou-AIE-TPP 探针是一种很有前途的 Aβ 聚集物荧光成像生物标志物开关，可用于监测 Aβ 诱导的神经毒性过程中线粒体形态的改变和功能障碍，这可能为未来用于靶向早期 Aβ 诊断的有前景的 AIE 生物标志物的发展提供重要方向。
