TY - JOUR
T1 - Well-defined cross-linked antioxidant nanozymes for treatment of ischemic brain injury
AU - Manickam, Devika S.
AU - Brynskikh, Anna M.
AU - Kopanic, Jennifer L.
AU - Sorgen, Paul L.
AU - Klyachko, Natalia L.
AU - Batrakova, Elena V.
AU - Bronich, Tatiana K.
AU - Kabanov, Alexander V.
N1 - Funding Information:
This work was supported by the United States National Institutes of Health (NIH) grant no. RR021937 , the Center for Biomedical Research Excellence (COBRE) Nebraska Center for Nanomedicine , grant no. 1RO1 NS057748 (to E V Batrakova), and the Ministry of Education and Science of Russian Federation grant no. 11.G34.31.0004 . We would like to thank the COBRE Nanomaterials Core Characterization Facility (Mr. Nazar Filonov), UNMC AFM core facility, EPR Spectroscopy Facility, and members of Kabanov's laboratory Dr. Xiang Yi and Mr. Marc R. Ueda for helpful discussions and Dr. Daria Y. Filonova (Alakhova) for help with schematic representation.
PY - 2012/9/28
Y1 - 2012/9/28
N2 - Development of well-defined nanomedicines is critical for their successful clinical translation. A simple synthesis and purification procedure is established for chemically cross-linked polyion complexes of Cu/Zn superoxide dismutase (SOD1) or catalase with a cationic block copolymer, methoxy-poly(ethylene glycol)-block-poly(L-lysine hydrochloride) (PEG-pLL 50). Such complexes, termed cross-linked nanozymes (cl-nanozymes) retain catalytic activity and have narrow size distribution. Moreover, their cytotoxicity is decreased compared to non-cross-linked complexes due to suppression of release of the free block copolymer. SOD1 cl-nanozymes exhibit prolonged ability to scavenge experimentally induced reactive oxygen species (ROS) in cultured brain microvessel endothelial cells and central neurons. In vivo they decrease ischemia/reperfusion-induced tissue injury and improve sensorimotor functions in a rat middle cerebral artery occlusion (MCAO) model after a single intravenous (i.v.) injection. Altogether, well-defined cl-nanozymes are promising modalities for attenuation of oxidative stress after brain injury.
AB - Development of well-defined nanomedicines is critical for their successful clinical translation. A simple synthesis and purification procedure is established for chemically cross-linked polyion complexes of Cu/Zn superoxide dismutase (SOD1) or catalase with a cationic block copolymer, methoxy-poly(ethylene glycol)-block-poly(L-lysine hydrochloride) (PEG-pLL 50). Such complexes, termed cross-linked nanozymes (cl-nanozymes) retain catalytic activity and have narrow size distribution. Moreover, their cytotoxicity is decreased compared to non-cross-linked complexes due to suppression of release of the free block copolymer. SOD1 cl-nanozymes exhibit prolonged ability to scavenge experimentally induced reactive oxygen species (ROS) in cultured brain microvessel endothelial cells and central neurons. In vivo they decrease ischemia/reperfusion-induced tissue injury and improve sensorimotor functions in a rat middle cerebral artery occlusion (MCAO) model after a single intravenous (i.v.) injection. Altogether, well-defined cl-nanozymes are promising modalities for attenuation of oxidative stress after brain injury.
KW - Antioxidant enzymes
KW - Block ionomer complexes
KW - Blood-brain barrier
KW - Cross-linked nanozymes
KW - Stroke therapy
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U2 - 10.1016/j.jconrel.2012.07.044
DO - 10.1016/j.jconrel.2012.07.044
M3 - Article
C2 - 22902590
AN - SCOPUS:84865811163
VL - 162
SP - 636
EP - 645
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 3
ER -