title: Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells.
abstract: BACKGROUND
  Our laboratories forged the concept of macrophage delivery of protein antioxidants to attenuate neuroinflammation and nigrostriatal neurodegeneration in Parkinson's disease. Notably, the delivery of the redox enzyme, catalase, incorporated into a polyion complex micelle ('nanozyme') by bone marrow-derived macrophages protected nigrostriatum against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. Nonetheless, how macrophage delivery of nanozyme increases the efficacy of catalase remains unknown.
  
  
  METHODS
  In this study, we examined the transfer of nanozyme from macrophages to brain microvessel endothelial cells, neurons and astrocytes.
  
  
  RESULTS
  Facilitated transport of the nanozyme from macrophages to endothelial, neuronal and glial target cells occurred through endocytosis-independent mechanisms that involved fusion of cellular membranes, macrophage bridging conduits and nanozyme lipid coatings. Nanozyme transfer was operative across an artificial blood-brain barrier and showed efficient reactive oxygen species decomposition.
  
  
  CONCLUSIONS
  This is the first demonstration, to our knowledge, that drug-loaded macrophages discharge particles to contiguous target cells for therapeutic brain enzyme delivery. The data shown are of potential value for the treatment of neurodegenerative disorders and notably, Parkinson's disease.
authors: Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA.
authors: Matthew J
authors: MJ
authors: Haney
authors: Yuling
authors: Y
authors: Zhao
authors: Shu
authors: S
authors: Li
authors: Sheila M
authors: SM
authors: Higginbotham
authors: Stephanie L
authors: SL
authors: Booth
authors: Huai-Yun
authors: HY
authors: Han
authors: Joseph A
authors: JA
authors: Vetro
authors: R Lee
authors: RL
authors: Mosley
authors: Alexander V
authors: AV
authors: Kabanov
authors: Howard E
authors: HE
authors: Gendelman
authors: Elena V
authors: EV
authors: Batrakova
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D001921:Brain / Q000098:blood supply / Q000166:cytology*; D002374:Catalase / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D004705:Endocytosis; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D010300:Parkinson Disease / Q000188:drug therapy
chemical_list: D000975:Antioxidants; D002374:Catalase