title: Blood-borne macrophage-neural cell interactions hitchhike on endosome networks for cell-based nanozyme brain delivery.
abstract: BACKGROUND
  Macrophage-carried nanoformulated catalase ('nanozyme') attenuates neuroinflammation and protects nigrostriatal neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. This is facilitated by effective enzyme transfer from blood-borne macrophages to adjacent endothelial cells and neurons leading to the decomposition of reactive oxygen species.
  
  
  METHODS
  We examined the intra- and inter-cellular trafficking mechanisms of nanozymes by confocal microscopy. Improved neuronal survival mediated by nanozyme-loaded macrophages was demonstrated by fluorescence-activated cell sorting.
  
  
  RESULTS
  In macrophages, nanozymes were internalized mainly by clathrin-mediated endocytosis then trafficked to recycling endosomes. The enzyme is subsequently released in exosomes facilitated by bridging conduits. Nanozyme transfer from macrophages to adjacent cells by endocytosis-independent mechanisms diffusing broadly throughout the recipient cells. In contrast, macrophage-free nanozymes were localized in lysosomes following endocytic entry.
  
  
  CONCLUSIONS
  Facilitated transfer of nanozyme from cell to cell can improve neuroprotection against oxidative stress commonly seen during neurodegenerative disease processes.
authors.affiliation: University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Haney
authors.forename: Poornima
authors.initials: P
authors.lastname: Suresh
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhao
authors.forename: Georgette D
authors.initials: GD
authors.lastname: Kanmogne
authors.forename: Irena
authors.initials: I
authors.lastname: Kadiu
authors.forename: Marina
authors.initials: M
authors.lastname: Sokolsky-Papkov
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Klyachko
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Elena V
authors.initials: EV
authors.lastname: Batrakova
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D002374:Catalase / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D021381:Protein Transport
chemical_list: D002374:Catalase