Dual Aggregations of a Near-Infrared Aggregation-Induced Emission Luminogen for Enhanced Imaging of Alzheimer’s Disease

Abstract

Aggregation-induced emission (AIE) enables "Turn-On" imaging generally through single aggregation of the AIE luminogen (AIEgen). Dual aggregrations of the AIEgen might further enhance the imaging intensity and the consequent sensitivity. Herein, we rationally designed a near-infrared (NIR) AIEgen Ac-Trp-Glu-His-Asp-Cys(StBu)-Pra(QMT)-CBT (<b>QMT-CBT</b>) which, upon caspase1 (Cas1) activation, underwent a CBT-Cys click reaction to form cyclic dimers <b>QMT-Dimer</b> (the first aggregation) and assembled into nanoparticles (the second aggregation), turning the AIE signal "on" for enhanced imaging of Alzheimer's disease (AD). Molecular dynamics simulations validated that the fluorogen <b>QMT</b> in <b>QMT-NPs</b> stacked much tighter with each other than in the single aggregates of the control compound Ac-Trp-Glu-His-Asp-Cys(tBu)-Pra(QMT)-CBT (<b>QMT-CBT-Ctrl</b>). Dual aggregations of QMT rendered 1.9-, 1.7-, and 1.4-fold enhanced fluorescence intensities of its single aggregation in vitro, in cells, and in a living AD mouse model, respectively. We anticipate this smart fluorogen to be used for sensitive diagnosis of AD in the clinic in the near future.