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


CONCLUSIONS
These data support the importance of macrophage-based nanozyme carriage for Parkinson's disease therapies.
Brynskikh
Anna M
AM
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
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
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects; D002374:Catalase / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*
D004337:Drug Carriers; D018696:Neuroprotective Agents; D002374:Catalase
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