title: Macrophage delivery of therapeutic nanozymes in a murine model of Parkinson's disease.
abstract: BACKGROUND
  Parkinson's disease is a common progressive neurodegenerative disorder associated with profound nigrostriatal degeneration. Regrettably, no therapies are currently available that can attenuate disease progression. To this end, we developed a cell-based nanoformulation delivery system using the antioxidant enzyme catalase to attenuate neuroinflammatory processes linked to neuronal death.
  
  
  METHODS
  Nanoformulated catalase was obtained by coupling catalase to a synthetic polyelectrolyte of opposite charge, leading to the formation of a polyion complex micelle. The nanozyme was loaded into bone marrow macrophages and its transport to the substantia nigra pars compacta was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice.
  
  
  RESULTS
  Therapeutic efficacy of bone marrow macrophages loaded with nanozyme was confirmed by twofold reductions in microgliosis as measured by CD11b expression. A twofold increase in tyrosine hydroxylase-expressing dopaminergic neurons was detected in nanozyme-treated compared with untreated MPTP-intoxicated mice. Neuronal survival was confirmed by magnetic resonance spectroscopic imaging. Bone marrow macrophage-loaded catalase showed sustained release of the enzyme in plasma.
  
  
  CONCLUSIONS
  These data support the importance of macrophage-based nanozyme carriage for Parkinson's disease therapies.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Brynskikh
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhao
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Michael D
authors.initials: MD
authors.lastname: Boska
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Klyachko
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; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects; D002374:Catalase / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D004337:Drug Carriers; D018696:Neuroprotective Agents; D002374:Catalase
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