Macrophage Delivery of Therapeutic Nanozymes in a Murine Model of Parkinson's Disease

Overview

Journal Nanomedicine (Lond)

Specialty Biotechnology

Date 2010 Apr 17

PMID 20394532

Citations 68

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

Affiliations

Soon will be listed here.

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.

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