Design and synthesis of new theranostic agents for near-infrared imaging of beta-amyloid plaques and inhibition of beta-amyloid aggregation in Alzheimer's disease

作者：Dao, Pascal; Ye, Feifei; Du, Zhi Yun; Chen, Qian; Zhang, Kun; Dong, Chang Zhi; Meunier, Bernard; Chen, Huixiong^*

来源：Dyes and Pigments, 2017, 147: 130-140.

DOI：10.1016/j.dyepig.2017.07.071

• Alzheimer's disease
• Beta-amyloid
• Cytotoxicity
• NIRF imaging
• Inhibitors
• Theranostic agents

The presence of amyloid plaques predisposes clinical symptoms of cognitive impairment, which occurs much earlier than other clinical symptoms and plays a crucial role in the neuropathology of AD. Thus, developing probes for A beta species imaging could be used for early diagnosis of AD, and blocking the initial steps of A beta aggregation with small molecules has emerged as a valid disease-modifying therapy for A beta. Herein, we report the design, synthesis and evaluation of a series of new theranostic agents, which can simultaneously perform near infra-red imaging of A beta plaques, prevent self-aggregation of A beta monomer, disaggregate preformed A beta fibrils and play a protective effect on the toxicity of human neuroblastoma cells (SHSY5Y) induced by A beta(1-42). Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Importantly, these probes are found to have a high binding affinity toward A beta aggregates, to exhibit a large fluorescence enhancement upon interaction with A beta aggregates accompanied by a blueshift in the emission spectra of 20-40 nm and to show an excellent targeting ability for A beta plaques in slices of brain and eye containing retina tissue from double transgenic mice. These molecules show a promising potential as theranostic agents for the diagnosis and therapy of AD.

• 出版日期2017-12
• 单位广东工业大学