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


ABSTRACT: 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.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.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.These data support the importance of macrophage-based nanozyme carriage for Parkinson's disease therapies.

SUBMITTER: Brynskikh AM 

PROVIDER: S-EPMC2880389 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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

Brynskikh Anna M AM   Zhao Yuling Y   Mosley R Lee RL   Li Shu S   Boska Michael D MD   Klyachko Natalia L NL   Kabanov Alexander V AV   Gendelman Howard E HE   Batrakova Elena V EV  

Nanomedicine (London, England) 20100401 3


<h4>Background</h4>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.<h4>Methods</h4>Nanoformulated catalase was obtained by coupling catalase to a synthetic pol  ...[more]

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