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

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 (QMT-CBT) which, upon caspase1 (Cas1) activation, underwent a CBT-Cys click reaction to form cyclic dimers QMT-Dimer (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 QMT in QMT-NPs 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 (QMT-CBT-Ctrl). 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.