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.

Endothelial targeting of liposomes encapsulating SOD/catalase mimetic EUK-134 alleviates acute pulmonary inflammation

“…Use of nanocarrier drug delivery systems (e.g., PEGylation, liposomes, nanozymes) may extend the circulation lifetime of these compounds, particularly AOEs, and improve quenching of extracellular ROS [7-9]. However, this may not be sufficient for treating acute vascular oxidative stress, which appears to be highly associated with endothelial ROS.…”

“…Activated leukocytes release ROS in the milieu that can cause tissue damage [6]. Administration of antioxidant formulations, including antioxidant enzymes (AOEs) modified with PEG or PEG-containing pluronics and N-acetyl cysteine (NAC)-loaded liposomes, has been shown to mitigate some of the harmful effects of extracellular ROS [7-9]. However, ROS are also produced in intracellular compartments of the endothelial cells lining blood vessels in response to inflammatory mediators and other damage-associated signals [10, 11].…”

Nanoformulated copper/zinc superoxide dismutase exerts differential effects on glucose vs lipid homeostasis depending on the diet composition possibly via altered AMPK signaling

“…Nano was prepared in 10mM HEPES buffer (pH- 7.4) as reported by Manickam et al ., 2012 [13]. Briefly, native bovine erythrocyte SOD1 protein (Sigma-Aldrich, St. Louis, MO, USA) was mixed with poly L-lysine-polyethylene glycol copolymer (PEG-pLL50, Alamanda Polymers ™ , Huntsville, AL).…”

Co-Immobilization of Superoxide Dismutase with Catalase on Soft Microparticles Formed by Self-Assembly of Amphiphilic Poly(Aspartic Acid)

“…Cerium oxide nanoparticles/nanoceria emerged as a potent artificial redox enzyme [10]. Antioxidant enzymes were encapsulated in nano-carriers in order to increase the half-life and thus the efficacy of these enzymes [11][12][13]. Liposomes have been extensively investigated for the encapsulation of SODs, superoxide dismutase entrapped in long-circulating poly(ethyleneglycol) (PEG)-liposomes [14], liposomal formulations of Cu, Zn-superoxide dismutase [15], superoxide dismutase entrapped in liposome for oral administration [16], the entrapment of superoxide dismutase into mucoadhesive chitosan-coated liposomes [17].…”