Phenothiazine-based theranostic compounds for in vivo near-infared fluorescence imaging of beta-amyloid plaques and inhibition of A beta aggregation

摘要

A global burden of Alzheimer's disease (AD) has been growing over last decades. Evidence indicates that beta-amyloid (A beta) production and senile plaque deposition in the brain is causative in the onset of AD pathogenesis. It appears much earlier than cognitive decline and plays a key role in initiating and developing AD neuropathology. As such, there is an intense passion with discovering theranostic agents which make a significant impact in diagnostic and therapy. Herein, we report an investigation of novel phenothiazine-based compounds as promising potential theranostic agents for AD. Remarkably, they have exhibited a high binding affinity toward A beta aggregates, a good biostability and a strong increase in their fluorescence intensity with blue shift when interacting with A beta aggregates. Furthermore, they have been simultaneously applied to perform NIR in vivo imaging of beta-amyloid plaques in double transgenic AD mouse model, to prevent self-aggregation of A beta monomer from forming toxic oligmers and to reduce A beta-induced toxicity of human neuroblastoma cells (SH-SY5Y).