Enhancing myelin repair in experimental model of multiple sclerosis using immobilized chondroitinase ABC I on porous silicon nanoparticles.

Removal of chondroitin sulfate proteoglycans (CSPGs) with chondroitinase ABC I (ChABC) facilitates axonal plasticity, axonal regeneration and remyelination, following injury to the central nervous system (CNS). However, the ChABC rapidly undergoes thermal inactivity and needs to be injected repeatedly. Here this limitation was overcame by immobilizing the ChABC on porous silicon (PSi) nanoparticles (ChABC@PSi). The efficacy of immobilized ChABC on CSPGs level and the demyelination insult was assessed in mice corpora callosa demyelinated by 6 weeks cuprizone (CPZ) feeding. ChABC@PSi was able to reduce the amount of CSPGs two weeks after animals treatment. CSPGs digestion by ChABC@PSi reduced the extent of demyelinated area as well as the astrogliosis. Furthermore, ChABC@PSi treatment increased the number of newly generated oligodendrocyte lineage cells which imply for enhanced myelin repair. Our results showed that effective CSPGs digestion by ChABC@PSi enhanced remyelination in CPZ model. Accordingly, ChABC@PSi may have a great potential to be used for treatment of diseases like multiple sclerosis and spinal cord injury by promoting the regeneration of damaged nerves. Unlabelled Image • ChABC loaded on PSi (ChABC@PSi) was stable, in vitro and in vivo. • ChABC@PSi decreased CSPGs deposition in an animal model of multiple sclerosis. • ChABC@PSi reduced CPZ-induced reactive astrogliosis and the extent of demyelination in CC. • ChABC@PSi promoted remyelination by increasing the generation of oligodendrocyte lineage cells. [ABSTRACT FROM AUTHOR]