SOD1 nanozyme salvages ischemic brain by locally protecting cerebral vasculature

作者：Jiang Yuhang; Brynskikh Anna M; S Manickam Devika^*; Kabanov Alexander V

来源：Journal of Controlled Release, 2015, 213: 36-44.

DOI：10.1016/j.jconrel.2015.06.021

• Stroke
• Superoxide dismutase
• Thrombus
• Blood-brain barrier
• Neurovascular unit
• Passive targeting

Copper/zinc superoxide dismutase (CuZnSOD; SOD1) is widely considered as a potential therapeutic candidate for pathologies involving oxidative stress, but its application has been greatly hindered by delivery issues. In our previous study, nanoformulated SOD1 (cl-nanozyme) was shown to decrease infarct volume and improve sensorimotor functions after a single intravenous (IV) injection in a rat middle cerebral artery occlusion (MCAO) model of ischemia/reperfusion (I/R) injury (stroke). However, it remained unclear how cl-nanozyme was able to deliver SOD1 to the brain and exert therapeutic efficacy. The present study aims to answer this question by exploringmicro-distribution pattern of cl-nanozyme in the rat brain after stroke. Immunohistochemistry studies demonstrated cl-nanozyme co-localization with fibrin along damaged arteries and capillaries in the ischemic hemisphere. We further found that cl-nanozyme can be cross-linked into thrombi formed after I/R injury in the brain, and this effect is independent of animal species (rat/mouse) used for modeling I/R injury. This work is also the first report reinforcing therapeutic potential of cl-nanozyme in a well-characterized mouse MCAO model of I/R injury.

• 出版日期2015-9-10