Design of aggregation-induced emission-active fluorogen-based nanoparticles for imaging and scavenging Alzheimer's
1Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. d_xy@tju.edu.cn.
Abstract:
Photo-oxygenation has emerged as an effective modality for scavenging Alzheimer's amyloid-β (Aβ) plaques. However, limitations of the current photo-oxidants, such as low Aβ-targeting and single functionality, hinder the scavenging of Aβ plaques via photo-oxygenation. Herein, based on an aggregation-induced emission (AIE)-active fluorogen (named TPMD), we designed AIE photo-oxidant nanoparticles (T-LD NPs) for Aβ imaging, inhibition, and disaggregation. The T-LD NPs were prepared by the assembly of hydrophobic TPMD with an Aβ-targeting peptide (LPPFD, L) conjugated amphiphilic polymer (DSPE-PEG). Such T-LD NPs could specifically label Aβ plaques for image-guided therapy. Under laser irradiation, T-LD NPs generated a plethora of reactive oxygen species (ROS), including 1O2, ˙OH, and O2˙-, to oxygenate Aβ species, leading to the potent inhibition of Aβ fibrillization, and significant alleviation of Aβ-mediated neurotoxicity (36% to 10% at 20 μg mL-1). Notably, T-LD NPs could rapidly disaggregate mature Aβ fibrils into fractured β-sheet rich aggregates via photo-oxygenation, resulting in alleviated cytotoxicity. In vivo studies revealed that the photo-activated T-LD NPs scavenged amyloid plaques in the transgenic C. elegans strain CL2006 and extended the lifespan by 4 days. Taken together, this multifunctional T-LD NP integrated Aβ-targeting, near-infrared fluorescence imaging, and photo-oxygenation, provides a new strategy for the development of multifunctional AIE photo-oxidants for the treatment of Alzheimer's disease.
