TY - JOUR
T1 - A macrophage-nanozyme delivery system for Parkinson's disease
AU - Batrakova, Elena V.
AU - Li, Shu
AU - Reynolds, Ashley D.
AU - Mosley, R. Lee
AU - Bronich, Tatiana K.
AU - Kabanov, Alexander V.
AU - Gendelman, Howard E.
PY - 2007
Y1 - 2007
N2 - Selective delivery of antioxidants to the substantia nigra pars compacta (SNpc) during Parkinson's disease (PD) can potentially attenuate oxidative stress and as such increase survival of dopaminergic neurons. To this end, we developed a bone-marrow-derived macrophage (BMM) system to deliver catalase to PD-affected brain regions in an animal model of human disease. To preclude BMM-mediated enzyme degradation, catalase was packaged into a block ionomer complex with a cationic block copolymer, polyethyleneimine-poly(ethylene glycol) (PEI-PEG). The self-assembled catalase/PEI-PEG complexes, "nanozymes" , were ca. 60 to 100 nm in size, stable in pH and ionic strength, and retained antioxidant activities. Cytotoxicity was negligible over a range of physiologic nanozyme concentrations. Nanozyme particles were rapidly, 40-60 min, taken up by BMM, retained catalytic activity, and released in active form for greater than 24 h. In contrast, "naked" catalase was rapidly degraded. The released enzyme decomposed microglial hydrogen peroxide following nitrated alpha-synuclein or tumor necrosis factor alpha activation. Following adoptive transfer of nanozyme-loaded BMM to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine- intoxicated mice, ca. 0.6% of the injected dose were found in brain. We conclude that cell-mediated delivery of nanozymes can reduce oxidative stress in laboratory and animal models of PD.
AB - Selective delivery of antioxidants to the substantia nigra pars compacta (SNpc) during Parkinson's disease (PD) can potentially attenuate oxidative stress and as such increase survival of dopaminergic neurons. To this end, we developed a bone-marrow-derived macrophage (BMM) system to deliver catalase to PD-affected brain regions in an animal model of human disease. To preclude BMM-mediated enzyme degradation, catalase was packaged into a block ionomer complex with a cationic block copolymer, polyethyleneimine-poly(ethylene glycol) (PEI-PEG). The self-assembled catalase/PEI-PEG complexes, "nanozymes" , were ca. 60 to 100 nm in size, stable in pH and ionic strength, and retained antioxidant activities. Cytotoxicity was negligible over a range of physiologic nanozyme concentrations. Nanozyme particles were rapidly, 40-60 min, taken up by BMM, retained catalytic activity, and released in active form for greater than 24 h. In contrast, "naked" catalase was rapidly degraded. The released enzyme decomposed microglial hydrogen peroxide following nitrated alpha-synuclein or tumor necrosis factor alpha activation. Following adoptive transfer of nanozyme-loaded BMM to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine- intoxicated mice, ca. 0.6% of the injected dose were found in brain. We conclude that cell-mediated delivery of nanozymes can reduce oxidative stress in laboratory and animal models of PD.
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U2 - 10.1021/bc700184b
DO - 10.1021/bc700184b
M3 - Article
C2 - 17760417
AN - SCOPUS:34648843409
SN - 1043-1802
VL - 18
SP - 1498
EP - 1506
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 5
ER -