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

Devika S. Manickam, Anna M. Brynskikh, Jennifer L. Kopanic, Paul L. Sorgen, Natalia L. Klyachko, Elena V. Batrakova, Tatiana K. Bronich, Alexander V. Kabanov

Research output: Contribution to journalArticle

48 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)636-645
Number of pages10
JournalJournal of Controlled Release
Volume162
Issue number3
DOIs
StatePublished - Sep 28 2012

Keywords

  • Antioxidant enzymes
  • Block ionomer complexes
  • Blood-brain barrier
  • Cross-linked nanozymes
  • Stroke therapy

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Manickam, D. S., Brynskikh, A. M., Kopanic, J. L., Sorgen, P. L., Klyachko, N. L., Batrakova, E. V., Bronich, T. K., & Kabanov, A. V. (2012). Well-defined cross-linked antioxidant nanozymes for treatment of ischemic brain injury. Journal of Controlled Release, 162(3), 636-645. https://doi.org/10.1016/j.jconrel.2012.07.044