Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells

Matthew J. Haney, Yuling Zhao, Shu Li, Sheila M. Higginbotham, Stephanie L. Booth, Huai Yun Han, Joseph A. Vetro, R. Lee Mosley, Alexander V. Kabanov, Howard E. Gendelman, Elena V. Batrakova

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Background: Our laboratories forged the concept of macrophage delivery of protein antioxidants to attenuate neuroinflammation and nigrostriatal neurodegeneration in Parkinsons 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. Conclusion: 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, Parkinsons disease.

Original languageEnglish (US)
Pages (from-to)1215-1230
Number of pages16
JournalNanomedicine
Volume6
Issue number7
DOIs
StatePublished - Sep 1 2011

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Keywords

  • Parkinson's disease
  • bloodbrain barrier
  • bone marrow-derived macrophages
  • cell-mediated drug delivery
  • intercellular communication

ASJC Scopus subject areas

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

Cite this

Haney, M. J., Zhao, Y., Li, S., Higginbotham, S. M., Booth, S. L., Han, H. Y., Vetro, J. A., Mosley, R. L., Kabanov, A. V., Gendelman, H. E., & Batrakova, E. V. (2011). Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells. Nanomedicine, 6(7), 1215-1230. https://doi.org/10.2217/nnm.11.32