Magnetite/Ceria Nanoparticle Assemblies for Extracorporeal Cleansing of Amyloid‐β in Alzheimer's Disease

Accumulation of amyloid‐β (Aβ) peptides in the brain is regarded as a major contributor to the pathogenesis and progression of Alzheimer's disease (AD). However, development of clinically relevant techniques to reduce Aβ levels in AD patients is hindered by low efficiency and/or side effects. Here, an extracorporeal Aβ cleansing system, where multifunctional magnetite/ceria nanoparticle assemblies are used to remove Aβ peptides from flowing blood by specific capture and magnetic separation, is reported. The magnetite nanoparticles in the nanoassembly core enable the magnetic isolation of the captured Aβ peptides by generating a large attraction force under an external magnetic field. The ceria nanoparticles in the nanoassembly shell relieve oxidative stress by scavenging reactive oxygen species that are produced by immune response during the process. Blood Aβ cleansing treatment of 5XFAD transgenic mice not only demonstrates the decreased Aβ levels both in the blood and in the brain but also prevents the spatial working memory deficits, suggesting the potential of the method for AD prevention and therapy.

[1]  S. Gambhir,et al.  An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo , 2018, Nature Biomedical Engineering.

[2]  W. Tremel,et al.  A Step into the Future: Applications of Nanoparticle Enzyme Mimics. , 2018, Chemistry.

[3]  T. Hyeon,et al.  Ceria Nanoparticle Systems for Selective Scavenging of Mitochondrial, Intracellular, and Extracellular Reactive Oxygen Species in Parkinson's Disease. , 2018, Angewandte Chemie.

[4]  S. Gourmaud,et al.  Brimapitide Reduced Neuronal Stress Markers and Cognitive Deficits in 5XFAD Transgenic Mice. , 2018, Journal of Alzheimer's disease : JAD.

[5]  Xiaoyuan Chen,et al.  Nanotechnology for Multimodal Synergistic Cancer Therapy. , 2017, Chemical reviews.

[6]  Jianlin Shi,et al.  Tumor-selective catalytic nanomedicine by nanocatalyst delivery , 2017, Nature Communications.

[7]  T. Hyeon,et al.  Multiplexible Wash-Free Immunoassay Using Colloidal Assemblies of Magnetic and Photoluminescent Nanoparticles. , 2017, ACS nano.

[8]  Chen Wang,et al.  Antibody‐Mimetic Peptoid Nanosheet for Label‐Free Serum‐Based Diagnosis of Alzheimer's Disease , 2017, Advanced materials.

[9]  Xiaoyuan Chen,et al.  Rethinking cancer nanotheranostics. , 2017, Nature reviews. Materials.

[10]  Dalong Ni,et al.  Magnesium silicide nanoparticles as a deoxygenation agent for cancer starvation therapy. , 2017, Nature nanotechnology.

[11]  Serena Mazzucchelli,et al.  Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies , 2016, Nature Communications.

[12]  Roland Riek,et al.  The activities of amyloids from a structural perspective , 2016, Nature.

[13]  K. Rhodes,et al.  The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease , 2016, Nature.

[14]  T. Hyeon,et al.  Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer's Disease. , 2016, ACS nano.

[15]  Guanghui Ma,et al.  Nanotheranostics: Congo Red/Rutin‐MNPs with Enhanced Magnetic Resonance Imaging and H2O2‐Responsive Therapy of Alzheimer's Disease in APPswe/PS1dE9 Transgenic Mice , 2015, Advanced materials.

[16]  Raimo Hartmann,et al.  In vivo integrity of polymer-coated gold nanoparticles. , 2015, Nature nanotechnology.

[17]  Donald E Ingber,et al.  An extracorporeal blood-cleansing device for sepsis therapy , 2014, Nature Medicine.

[18]  Nick C Fox,et al.  Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. , 2014, The New England journal of medicine.

[19]  E. Siemers,et al.  Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. , 2014, The New England journal of medicine.

[20]  E. Wang,et al.  Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. , 2013, Chemical Society reviews.

[21]  Chenjie Xu,et al.  New forms of superparamagnetic nanoparticles for biomedical applications. , 2013, Advanced drug delivery reviews.

[22]  Dohoung Kim,et al.  Ceria nanoparticles that can protect against ischemic stroke. , 2012, Angewandte Chemie.

[23]  Xiaogang Qu,et al.  Using Graphene Oxide High Near‐Infrared Absorbance for Photothermal Treatment of Alzheimer's Disease , 2012, Advanced materials.

[24]  L. Mucke,et al.  Alzheimer Mechanisms and Therapeutic Strategies , 2012, Cell.

[25]  B. Strooper,et al.  The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics , 2011, Nature Reviews Drug Discovery.

[26]  J. Carrero,et al.  Monitoring of inflammation in patients on dialysis: forewarned is forearmed , 2011, Nature Reviews Nephrology.

[27]  M. Ohno,et al.  Partial reduction of BACE1 improves synaptic plasticity, recent and remote memories in Alzheimer’s disease transgenic mice , 2010, Journal of neurochemistry.

[28]  E. Masliah,et al.  Can Alzheimer disease be prevented by amyloid-β immunotherapy? , 2010, Nature Reviews Neurology.

[29]  Boris Murmann,et al.  Matrix-insensitive protein assays push the limits of biosensors in medicine , 2009, Nature Medicine.

[30]  Bing Xu,et al.  Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications. , 2009, Accounts of chemical research.

[31]  R. Deane,et al.  Clearance of amyloid-β peptide across the blood-brain barrier: Implication for therapies in Alzheimer’s disease , 2009 .

[32]  Robert L White,et al.  Multiplex protein assays based on real-time magnetic nanotag sensing , 2008, Proceedings of the National Academy of Sciences.

[33]  M. Ohno,et al.  Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation , 2006, The Journal of Neuroscience.

[34]  David M Holtzman,et al.  Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo , 2006, Nature Medicine.

[35]  Bing Xu,et al.  Biofunctional magnetic nanoparticles for protein separation and pathogen detection. , 2006, Chemical communications.

[36]  M. Mattson Pathways towards and away from Alzheimer's disease , 2004, Nature.

[37]  Hao Zeng,et al.  Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles. , 2004, Journal of the American Chemical Society.

[38]  J. Hardy,et al.  The Amyloid Hypothesis of Alzheimer ’ s Disease : Progress and Problems on the Road to Therapeutics , 2009 .

[39]  D. Holtzman,et al.  Brain to Plasma Amyloid-β Efflux: a Measure of Brain Amyloid Burden in a Mouse Model of Alzheimer's Disease , 2002, Science.

[40]  S. Younkin,et al.  Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice , 1996, Science.