A theranostic agent for in vivo near-infrared imaging of β-amyloid species and inhibition of β-amyloid aggregation
A theranostic agent for in vivo near-infrared imaging of β-amyloid species and inhibition of β-amyloid aggregation
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DOI：
10.1016/j.biomaterials.2016.03.047
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发表时间：
2016-07-01
期刊：
影响因子：
14
通讯作者：
Wong, Man Shing
中科院分区：
文献类型：
--
作者：
Li, Yinhui;Xu, Di;Wong, Man Shing
β-淀粉样蛋白（A β）肽作为老年斑的主要成分之一，与难治性阿尔茨海默病（AD）的发生、发展密切相关。已经进行了大量努力来开发用于AD诊断的A β种类/斑块成像的探针，并开发用于治疗的防止有毒可溶性寡聚A β形成的聚集抑制剂。在此，首次报道了一系列新型带电分子，其可以同时在动物模型中进行A β种类/斑块的近红外体内成像和抑制A β单体形成毒性寡聚体的自聚集。其中，DBA-SLOH由于在带电骨架中引入了中等长度的亲脂性烷基链，因此表现出优异的血脑屏障（BBB）渗透性和生物相容性。重要的是，发现DBA-SLOH对AB种类具有高结合亲和力，在与所有种类相互作用后表现出显著的荧光增强。尽管与A β聚集体相比与A β单体的结合较弱，但DBA-SLOH可有效地防止A β（1-40）和A β（1-42）肽自聚集并形成毒性寡聚体。这种多功能荧光分子显示出作为诊断和治疗AD的治疗诊断剂的有希望的潜力。(C)2016爱思唯尔有限公司版权所有
Amyloid-beta (A beta) peptide as one of the main components of senile plaques is closely related to the onset and progression of incurable Alzheimer's disease (AD). Numerous efforts have been devoted to develop probes for A beta species/plaque imaging for AD diagnostics and to develop aggregation inhibitors preventing formation of toxic soluble oligomeric A beta for therapeutics. Herein, for the first time, a series of novel charged molecules, which can simultaneously perform near infra-red in vivo imaging of A beta species/plaques in animal model and inhibition of self-aggregation of A beta monomer from forming toxic oligomers, are reported. Among them, DBA-SLOH showed excellent blood-brain barrier (BBB) permeability and biocompatibility due to the incorporation of lipophilic alkyl chains with moderate length into the charged skeleton. Importantly, DBA-SLOH was found to have a high binding affinity toward AB species exhibiting a dramatic fluorescence enhancement upon interacting with All species. Despite a weaker binding with A beta monomers as compared to A beta aggregates, DBA-SLOH could effectively prevent the A beta(1-40) and A beta(1-42) peptides from self-aggregation and forming toxic oligomers. This multifunctional fluorescent molecule shows promising potential as a theranostic agent for the diagnosis and therapy of AD. (C) 2016 Elsevier Ltd. All rights reserved.