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 Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Anal Chem. 2021 Sep 21;93(37):12617-12627. doi: 10.1021/acs.analchem.1c02289. Epub 2021 Sep 8.
Alzheimer's disease (AD) is a neurodegenerative disease, and β-amyloid (Aβ) is believed to be a causative factor in AD pathology. The abnormal deposition of Aβ is believed to be responsible for progression of AD. In order to facilitate the imaging of Aβ , suitable probe molecules with a near-infrared emission wavelength that can penetrate the blood-brain barrier (BBB) were utilized. The commercial fluorescent probe thioflavin-T (ThT) is used to image Aβ; however, because of its short emission wavelength and poor BBB penetration, ThT can only be used . With this research, based on ThT, we design three fluorescent probes (SZIs) having a longer emission wavelength in order to image Aβ aggregates. SZIs with different numbers of double bonds respond to Aβ aggregates. The SZIs have a structure similar to ThT, and as such, the SZIs are also unable to penetrate the BBB. To deal with the problem, we develop nanocomposites (MSN-Lf@SZIs) to deliver SZIs into the brain of AD mouse and image Aβ successfully. These new nanocomposites are able to deliver the dyes into the brain and facilitate Aβ imaging .
阿尔茨海默病（AD）是一种神经退行性疾病，β-淀粉样蛋白（Aβ）被认为是 AD 病理学的致病因素。Aβ的异常沉积被认为是 AD 进展的原因。为了便于 Aβ的成像，利用了具有近红外发射波长的合适的探针分子，该波长可以穿透血脑屏障（BBB）。商用荧光探针硫黄素-T（ThT）用于成像 Aβ；然而，由于其发射波长较短且穿透 BBB 的能力较差，因此只能使用 ThT。有鉴于此，基于 ThT，我们设计了三种具有更长发射波长的荧光探针（SZIs），以便对 Aβ 聚集体进行成像。具有不同双键数的 SZIs 对 Aβ聚集体有响应。SZIs 的结构与 ThT 相似，因此 SZIs 也无法穿透 BBB。为了解决这个问题，我们开发了纳米复合材料（MSN-Lf@SZIs），将 SZIs 递送至 AD 小鼠的大脑中，并成功地对 Aβ进行成像。这些新型纳米复合材料能够将染料递送至大脑并促进 Aβ的成像。
