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

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.

• Authors: Devika S Manickam, Anna M Brynskikh, Jennifer L Kopanic, Paul L Sorgen, Natalia L Klyachko, Elena V Batrakova, Tatiana K Bronich, Alexander V Kabanov
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 162 Issue 3 Pg. 636-45 (Sep 28 2012) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 22902590 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Cross-Linking Reagents
• Succinimides
• mPEG-block-PLL
• Polylysine
• Polyethylene Glycols
• 3,3'-dithiobis(sulfosuccinimidyl propionate)
• Catalase
• Superoxide Dismutase

Topics

• Animals
• Antioxidants (administration & dosage, chemistry)
• Catalase (administration & dosage, chemistry)
• Cattle
• Cell Line
• Cross-Linking Reagents (chemistry)
• Infarction, Middle Cerebral Artery (drug therapy, physiopathology)
• Male
• Polyethylene Glycols (chemistry)
• Polylysine (analogs & derivatives, chemistry)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, physiopathology)
• Succinimides (chemistry)
• Superoxide Dismutase (administration & dosage, chemistry)