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

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• 作者：Devika S. Manickam ; Anna M. Brynskikh ; Jennifer L. Kopanic ; Paul L. Sorgen ; Natalia L. Klyachko ; Elena V. Batrakova ; Tatiana K. Bronich ; Alex ; er V. Kabanov
• 关键词：Antioxidant enzymes ; Block ionomer complexes ; Blood&ndash ; brain barrier ; Cross-linked nanozymes ; Stroke therapy
• 刊名：Journal of Controlled Release
• 出版年：2012
• 出版时间：28 September, 2012
• 年：2012
• 卷：162
• 期：3
• 页码：636-645
• 全文大小：883 K

文摘

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.