Эксосомная совместная доставка супероксидной дисмутазы и хондроитиназы ABC для многократной склерозовой терапии.

Exosome-mediated co-delivery of superoxide dismutase and chondroitinase ABC for multiple sclerosis therapy.

Multiple sclerosis is an autoimmune demyelinating disease, and its effective treatment is a great challenge. As a typical animal model for studying multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) is characterized by inflammation, demyelination, gliosis and axonal loss. Thus, simultaneous regulation of neuroinflammation and remyelination may be a useful strategy against EAE. Herein, superoxide dismutase (SOD) and chondroitinase ABC (ChABC) were co-encapsulated in exosomes to obtain SOD and ChABC-loaded exosomes (SOD/ChABC@EXO) to investigate whether the combination of therapeutic enzymes was effective in the treatment of EAE. The SOD/ChABC@EXO was found to possess high SOD and ChABC activities, which could scavenge intracellular reactive oxygen species and inhibit the apoptosis of lipopolysaccharide-activated BV2 cells. Meanwhile, intranasal administration of SOD/ChABC@EXO could achieve the high accumulation of enzyme molecules in spinal cord and brain, and manifest the modulation of neuroinflammation and remyelination in EAE mice model. Overall, the exosome-mediated intranasal co-delivery of SOD and ChABC provides a potential strategy to treat multiple sclerosis.