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J Control Release. 2012 Sep 28;162(3):636-45. doi: 10.1016/j.jconrel.2012.07.044. Epub 2012 Aug 10.

Well-defined cross-linked antioxidant nanozymes for treatment of ischemic brain injury.

Author information

1
Department of Pharmaceutical Sciences, University of Nebraska Medical Center-UNMC, Omaha, NE 68198, USA. dsmanickam@gmail.com

Abstract

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-pLL₅₀). 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.

PMID:
22902590
PMCID:
PMC3597468
DOI:
10.1016/j.jconrel.2012.07.044
[Indexed for MEDLINE]
Free PMC Article
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