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 Eliot Gendelman, Elena V. Batrakova

Research output: Contribution to journalArticle

84 Citations (Scopus)

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 1 2010

Fingerprint

Macrophages
Catalase
Parkinson Disease
bone
Disease
Bone
Bone Marrow
enzyme
Enzymes
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
antioxidant
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Micelles
Magnetic resonance
Therapeutics
Antioxidants
Polyelectrolytes
Catalyst supports
Neurodegenerative Diseases

Keywords

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

ASJC Scopus subject areas

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

Cite this

Brynskikh, A. M., Zhao, Y., Mosley, R. L., Li, S., Boska, M. D., Klyachko, N. L., ... 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

Macrophage delivery of therapeutic nanozymes in a murine model of Parkinsons disease. / Brynskikh, Anna M.; Zhao, Yuling; Mosley, R Lee; Li, Shu; Boska, Michael D.; Klyachko, Natalia L.; Kabanov, Alexander V.; Gendelman, Howard Eliot; Batrakova, Elena V.

In: Nanomedicine, Vol. 5, No. 3, 01.04.2010, p. 379-396.

Research output: Contribution to journalArticle

Brynskikh, AM, Zhao, Y, Mosley, RL, Li, S, Boska, MD, Klyachko, NL, Kabanov, AV, Gendelman, HE & Batrakova, EV 2010, 'Macrophage delivery of therapeutic nanozymes in a murine model of Parkinsons disease', Nanomedicine, vol. 5, no. 3, pp. 379-396. https://doi.org/10.2217/nnm.10.7
Brynskikh, Anna M. ; Zhao, Yuling ; Mosley, R Lee ; Li, Shu ; Boska, Michael D. ; Klyachko, Natalia L. ; Kabanov, Alexander V. ; Gendelman, Howard Eliot ; Batrakova, Elena V. / Macrophage delivery of therapeutic nanozymes in a murine model of Parkinsons disease. In: Nanomedicine. 2010 ; Vol. 5, No. 3. pp. 379-396.
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