Multiple effects of polydopamine nanoparticles on Cu^(2+)-mediated Alzheimer's β-amyloid aggregation  

作　　者：Xueqing Chen Weiqun Gao Yan Sun Xiaoyan Dong 

机构地区：[1]Department 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

出　　处：《Chinese Journal of Chemical Engineering》2023年第2期144-152,共9页中国化学工程学报（英文版）

基　　金：funded by the National Natural Science Foundation of China (21978207 and 21621004);the Natural Science Foundation of Tianjin from Tianjin Municipal Science and Technology Commission (19JCZDJC36800)。

摘　　要：Deposition of β-amyloid protein(Aβ) is the main hallmark of Alzheimer's disease(AD), and it has been well recognized that Cu^(2+)-mediated Aβ aggregation plays a crucial role in AD pathological processes.Cu^(2+)binding to Aβ can promote the production of reactive oxygen species(ROS) through Fenton-like reactions and produce more toxic Aβ-Cu^(2+)species under Cu^(2+)stimulation. Thus, the development of nanomaterials that can inhibit Cu^(2+)-mediated Aβ aggregation and degrade Aβ-Cu^(2+)complexes is considered an effective strategy for the prevention and treatment of AD. In this study, polydopamine nanoparticles(PDA NPs) were prepared and the results reveal that PDA NPs potently inhibit Cu^(2+)-mediated Aβaggregation and effectively reduce the formation of Aβ-Cu^(2+)complexes. In vitro experiments show that PDA NPs efficiently eliminate ROS generation catalyzed by Cu^(2+)or Aβ-Cu^(2+)complexes, thus rescuing cultured cells by reducing intracellular ROS levels. More importantly, PDA NPs can depolymerize Aβ-Cu^(2+)complexes, and the degradation of Aβ-Cu^(2+)complexes is promoted by near-infrared light irradiation due to their high photothermal conversion ability. In vivo studies reveal that PDA NPs significantly reduce the deposition of Aβ plaques in the presence of Cu^(2+)and extend the lifespan of AD nematodes from 11 to 14 d. Thus, the PDA NPs developed herein are multifunctional against Cu^(2+)-mediated Aβ aggregation for the potential prevention and treatment of AD.

关 键 词：Protein AGGREGATION NANOPARTICLES Photothermal therapy Reactive oxygen species Cu^(2+)chelator 

分 类 号：R749.16[医药卫生—神经病学与精神病学] TB383.1[医药卫生—临床医学]