Intranasal delivery of cerium oxide nanozyme and superoxide dismutase in exosomes for Parkinson's disease therapy.
Intranasal delivery of cerium oxide nanozyme and superoxide dismutase in exosomes for Parkinson's disease therapy.
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Original abstract
The excessive reactive oxygen species (ROS) play an important role in the occurrence and progression of Parkinson's disease (PD). To investigate whether the antioxidant enzymes can scavenge the ROS level in vivo and treat PD efficiently, superoxide dismutase (SOD) was encapsulated into HEK293-derived exosomes to prepare SOD-loaded exosomes (SOD@EXO), and catalase (CAT)-like cerium oxide nanozyme (CeO2) was mixed with SOD@EXO to construct the formulation, namely SOD@EXO + CeO2. The formulation with cup-shaped morphology showed high SOD and CAT activities, which could scavenge the ROS level in a cascade manner. In vitro neuroprotective trials against SH-SY5Y cells revealed that SOD@EXO + CeO2 could efficiently prevent the neurotoxicity in 1-methyl-4-phenylpyridine-induced PD cell model. Moreover, the exosomes could be significantly accumulated in brain after the intranasal administration in comparison to the intravenous injection. Finally, the system was found to ameliorate the behavior disorder and relieve the inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice model after the intranasal administration of SOD@EXO + CeO2. In a word, SOD@EXO + CeO2 could act in a cascade manner to scavege ROS, relieve the inflammatory response and improve the behavior disorder. Our results provide a new paradigm to construct the prevention and treatment strategy of dyskinesia diseases in central nervous system in future.