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 beta-amyloid (A beta) 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 A beta 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 A beta fibrosis and promotes fibril disassembly, thereby attenuating A beta-induced neurotoxicity. DNTPH treatment significantly reduced A beta 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 A beta plaques and AD therapy simultaneously.