Near‐Infrared Aggregation‐Induced Emission Luminogens for In Vivo Theranostics of Alzheimer's Disease. Issue 2 (2nd December 2022) - Zhang, Tianfu
Abstract: 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. Abstract : An aggregation‐induced emission (AIE) probe, DNTPH, was designed by balancing hydrophobic and hydrophilic moieties. DNTPH displays excellent blood–brain barrier permeability and binds to β‐amyloid Aβ42 fibrils selectively. Remarkably, DNTPH exhibits a strong inhibitory effect on Aβ fibrosis, thus attenuating Aβ‐induced neurotoxicity in Alzheimer's disease (AD) mice. DNTPH serves as the first AIE in vivo theranostic agent for near‐infrared imaging of Aβ42 plaques and AD therapy.