Macrophage delivery of therapeutic nanozymes in a murine model of Parkinsons disease

Anna M. Brynskikh, Yuling Zhao, R. Lee Mosley, Shu Li, Michael D. Boska, Natalia L. Klyachko, Alexander V. Kabanov, Howard E. Gendelman, Elena V. Batrakova

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Background: Parkinsons 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. Conclusion: These data support the importance of macrophage-based nanozyme carriage for Parkinsons disease therapies.

Original languageEnglish (US)
Pages (from-to)379-396
Number of pages18
JournalNanomedicine
Volume5
Issue number3
DOIs
StatePublished - Apr 2010

Keywords

  • Bloodbrain barrier
  • Catalase
  • Cell-mediated drug delivery
  • Neuroinflammation
  • Parkinsons disease

ASJC Scopus subject areas

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

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    Brynskikh, A. M., Zhao, Y., Mosley, R. L., Li, S., Boska, M. D., Klyachko, N. L., Kabanov, A. V., Gendelman, H. E., & Batrakova, E. V. (2010). Macrophage delivery of therapeutic nanozymes in a murine model of Parkinsons disease. Nanomedicine, 5(3), 379-396. https://doi.org/10.2217/nnm.10.7