Macrophage delivery of therapeutic nanozymes in a murine model of Parkinson's disease.

Abstract

BACKGROUND:

Parkinson's 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 Parkinson's disease therapies.

• Authors: 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
• Journal: Nanomedicine (London, England) (Nanomedicine (Lond)) Vol. 5 Issue 3 Pg. 379-96 (Apr 2010) ISSN: 1748-6963 [Electronic] England
• PMID: 20394532 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Drug Carriers
• Neuroprotective Agents
• Catalase

Topics

• Animals
• Bone Marrow Cells (cytology, drug effects, metabolism)
• Brain (drug effects)
• Catalase (administration & dosage, pharmacokinetics, therapeutic use)
• Cell Adhesion (drug effects)
• Cell Movement (drug effects)
• Drug Carriers (chemistry)
• Macrophages (cytology, drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Nanostructures (chemistry)
• Neuroprotective Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Oxidative Stress (drug effects)
• Parkinson Disease (drug therapy)