Plain-language summary
Reactive oxygen species accumulate in the brain in Parkinson's disease and contribute to the death of dopamine-producing neurons. Antioxidant enzymes such as superoxide dismutase (SOD) could in principle neutralize them, but enzymes are large, fragile molecules that cross the blood-brain barrier poorly. In this study, researchers loaded SOD into exosomes — small membrane vesicles naturally released by cells — derived from HEK293 cells, and combined them with a cerium oxide nanozyme that mimics catalase, another ROS-scavenging enzyme. The combined formulation cleared reactive oxygen species in a cascading manner, first converting superoxide to hydrogen peroxide and then breaking that down. In a cell model of Parkinson's disease, the formulation protected neuronal cells from toxin-induced damage. Notably, after intranasal administration in mice, the exosomes accumulated in the brain far more than after intravenous injection, and treated animals showed improved motor behavior and reduced brain inflammation.
Key findings
- Superoxide dismutase was encapsulated in HEK293-cell exosomes and paired with a catalase-mimicking cerium oxide nanozyme to clear reactive oxygen species in sequence.
- The formulation protected neuronal cells from toxin-induced damage in a Parkinson's disease cell model.
- Intranasal administration delivered the exosomes to the brain far more effectively than intravenous injection in mice.
- Treated mice showed improved behavior and reduced inflammatory responses in a Parkinson's disease model.
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.
Frequently asked questions
What did this study find?
Reactive oxygen species accumulate in the brain in Parkinson's disease and contribute to the death of dopamine-producing neurons. Antioxidant enzymes such as superoxide dismutase (SOD) could in principle neutralize them, but enzymes are large, fragile molecules that cross the blood-brain barrier poorly. In this study, researchers loaded SOD into exosomes — small membrane vesicles naturally released by cells — derived from HEK293 cells, and combined them with a cerium oxide nanozyme that mimics catalase, another ROS-scavenging enzyme. The combined formulation cleared reactive oxygen species in a cascading manner, first converting superoxide to hydrogen peroxide and then breaking that down. In a cell model of Parkinson's disease, the formulation protected neuronal cells from toxin-induced damage. Notably, after intranasal administration in mice, the exosomes accumulated in the brain far more than after intravenous injection, and treated animals showed improved motor behavior and reduced brain inflammation.
Was this tested in humans or in the laboratory?
This is delivery-science work, focused on how the vesicles behave when they are administered.
Where can I read the original paper?
The full text lives with the publisher: https://doi.org/10.1016/j.mtbio.2026.103629
How to cite this paper
Shao Xinxin, Li Kefei, Wang Yanbo, He Xinai, Xiong Boyu, Yang Shengcai et al.. Intranasal delivery of cerium oxide nanozyme and superoxide dismutase in exosomes for Parkinson's disease therapy.. Materials today. Bio. 2026, 2026-09-17. DOI: 10.1016/j.mtbio.2026.103629
Source & verification
- Journal: Materials today. Bio
- Published: 17 September 2026
- DOI: 10.1016/j.mtbio.2026.103629
- PubMed ID: 42750983
- Indexed via: pubmed
- MeSH terms: —