Blood-borne macrophage-neural cell interactions hitchhike on endosome networks for cell-based nanozyme brain delivery

Matthew J. Haney, Poornima Suresh, Yuling Zhao, Georgette D. Kanmogne, Irena Kadiu, Marina Sokolsky-Papkov, Natalia L. Klyachko, R. Lee Mosley, Alexander V. Kabanov, Howard E. Gendelman, Elena V. Batrakova

Research output: Contribution to journalArticle

30 Scopus citations

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. Materials & 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. Conclusion: Facilitated transfer of nanozyme from cell to cell can improve neuroprotection against oxidative stress commonly seen during neurodegenerative disease processes. Original submitted 29 June 2011; Revised submitted 14 September 2011; Published online 11 January 201.

Original languageEnglish (US)
Pages (from-to)815-833
Number of pages19
JournalNanomedicine
Volume7
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Parkinsons disease
  • blood-brain barrier
  • catalase
  • cell-mediated drug delivery
  • exosome
  • intracellular localization
  • macrophage
  • nanozyme

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

Fingerprint Dive into the research topics of 'Blood-borne macrophage-neural cell interactions hitchhike on endosome networks for cell-based nanozyme brain delivery'. Together they form a unique fingerprint.

  • Cite this

    Haney, M. J., Suresh, P., Zhao, Y., Kanmogne, G. D., Kadiu, I., Sokolsky-Papkov, M., Klyachko, N. L., Mosley, R. L., Kabanov, A. V., Gendelman, H. E., & Batrakova, E. V. (2012). Blood-borne macrophage-neural cell interactions hitchhike on endosome networks for cell-based nanozyme brain delivery. Nanomedicine, 7(6), 815-833. https://doi.org/10.2217/nnm.11.156