title: Ceria/POMs hybrid nanoparticles as a mimicking metallopeptidase for treatment of neurotoxicity of amyloid-β peptide.
abstract: Protein misfolding to amyloid aggregates is the hallmark for neurodegenerative disease. While much attention has been paid to screen natural proteases that can degrade amyloid-β peptides (Aβ), it is difficult to apply them in the clinics with the intractable problem of immunogenicity in living organisms. Herein, we rationally designed an artificial nanozyme, Ceria/Polyoxometalates hybrid (CeONP@POMs) with both proteolytic and superoxide dismutase (SOD) activities. Our results indicated that CeONP@POMs could efficiently degrade Aβ aggregates and reduce intracellular reactive oxygen species (ROS). More importantly, CeONP@POMD could not only promote PC12 cell proliferation and can cross blood-brain barrier (BBB), but also inhibit Aβ-induced BV2 microglial cell activation which was demonstrated by immunoluorescence assay and flow cytometry measurements. In vivo studies further indicated that CeONP@POMD as nanozyme possessed good biocompatibility, evidenced by a detailed study of their biodistribution, body weight change, and in vivo toxicology. Therefore, our results pave the way for design of multifunctional artificial nanozyme for treatment of neurotoxicity of amyloid-β peptide.
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China; University of Chinese Academy of Sciences, Beijing 1000039, China.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Dong
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Gao
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Biochemistry and Molecular Biology Central Laboratory, The Second Hospital of Jilin University, Changchun 130041, China.
authors.forename: Yongchen
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Laboratory of Chemical Biology, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China. Electronic address: xqu@ciac.ac.cn.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Qu
mesh_terms: D016229:Amyloid beta-Peptides / Q000627:therapeutic use / Q000633:toxicity* / Q000648:ultrastructure; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002563:Cerium / Q000737:chemistry*; D006868:Hydrolysis; D045726:Metalloproteases / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D053758:Nanoparticles / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D017973:Tungsten Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D000099294:Polyoxometalates
chemical_list: D016229:Amyloid beta-Peptides; D002563:Cerium; D045726:Metalloproteases; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D017973:Tungsten Compounds; C102296:polyoxometalate I; D000099294:Polyoxometalates; C030583:ceric oxide
keywords: Alzheimer's disease; Amyloid-β peptides; Hydrolytic activity; Nanozyme; Polyoxometalates