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

作者：Manickam Devika S^*; Brynskikh Anna M; Kopanic Jennifer L; Sorgen Paul L; Klyachko Natalia L; Batrakova Elena V; Bronich Tatiana K; Kabanov Alexander V

来源：Journal of Controlled Release, 2012, 162(3): 636-645.

DOI：10.1016/j.jconrel.2012.07.044

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

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.

• 出版日期2012-9-28