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.

DOI: 10.2217/nnm.10.7
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@article{Brynskikh2010MacrophageDO, title={Macrophage delivery of therapeutic nanozymes in a murine model of Parkinson's disease.}, author={Anna M Brynskikh and Yuling Zhao and Rodney Lee Mosley and Shu Li and Michael D. Boska and Natalia L. Klyachko and Alexander V. Kabanov and Howard E. Gendelman and Elena V. Batrakova}, journal={Nanomedicine}, year={2010}, volume={5 3}, pages={379-96} }