Near-Infrared Aggregation-Induced Emission Luminogens for In Vivo Theranostics of Alzheimer's Disease.

Optimized theranostic strategies for Alzheimer's disease (AD) remain almost absent from bench to clinic. Current probes and drugs attempting to prevent β-amyloid (Aβ) fibrosis encounter failures due to the blood-brain barrier (BBB) penetration challenge and blind intervention time window. Herein, we design a near-infrared (NIR) aggregation-induced emission (AIE) probe, DNTPH, via balanced hydrophobicity-hydrophilicity strategy. DNTPH binds selectively to Aβ fibrils with a high signal-to-noise ratio. In vivo imaging revealed its excellent BBB permeability and long-term tracking ability with high-performance AD diagnosis. Remarkably, DNTPH exhibits a strong inhibitory effect on Aβ fibrosis and promotes fibril disassembly, thereby attenuating Aβ-induced neurotoxicity. DNTPH treatment significantly reduced Aβ plaques and rescued learning deficits in AD mice. Thus, DNTPH serves as the first AIE in vivo theranostic agent for real-time NIR imaging of Aβ plaques and AD therapy simultaneously.