Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's disease
The application of extracellular vesicles (EVs) as vehicles for anti-Parkinson's agents represents a significant advance, yet their clinical translation is hampered by challenges in efficient brain delivery and complex blood-brain barrier (BBB) targeting strategies. In this study, we engineered dopamine onto the surface of adipose-derived stem cell EVs (Dopa-EVs) utilizing a facile, two-step cross-linking approach. This engineering enhanced neuronal uptake of the EVs in primary neurons and neuroblastoma cells, a process shown to be competitively inhibited by dopamine pretreatment and dopamine receptor antibodies. Notably, Dopa-EVs demonstrated increased brain accumulation in mouse Parkinson's disease (PD) models. Therapeutically, Dopa-EVs administration led to the rescue of dopaminergic neuronal loss and amelioration of behavioural deficits in both 6-hydroxydopamine (6-OHDA) and α-Syn PFF-induced PD models. Furthermore, we observed that Dopa-EVs stimulated autophagy evidenced by the upregulation of Beclin-1 and LC3-II. These findings collectively indicate that surface modification of EVs with dopamine presents a potent strategy for targeting dopaminergic neurons in the brain. The remarkable therapeutic potential of Dopa-EVs, demonstrated in PD models, positions them as a highly promising candidate for PD treatment, offering a significant advance over current therapeutic modalities.
Authors
- Donghoon Ahn (ORCID: https://orcid.org/0000-0002-6868-9161)
- Junsik Kim (ORCID: https://orcid.org/0000-0002-0287-9640)
- Jeongyun Kim (ORCID: https://orcid.org/0000-0003-4085-5444)
- Jae Hoon Sul (ORCID: https://orcid.org/0000-0002-0862-7057)
- Dong‐Gyu Jo (ORCID: https://orcid.org/0000-0003-2271-1076)
- L. Palomera (ORCID: https://orcid.org/0000-0002-7608-447X)
- Jungmi Lee (ORCID: https://orcid.org/0000-0001-6277-1423)
- Jihoon Han (ORCID: https://orcid.org/0000-0001-5870-1414)
- Seung Hyun Baek (ORCID: https://orcid.org/0000-0002-4863-5529)
- Ka Young Chung (ORCID: https://orcid.org/0000-0001-9038-9571)
- Tae‐In Kam (ORCID: https://orcid.org/0000-0002-7241-4902)
- Sol Shin (ORCID: https://orcid.org/0000-0002-3261-1928)
- C.H. Kim (ORCID: https://orcid.org/0009-0001-0935-4134)
- Sun Young Park (ORCID: https://orcid.org/0000-0002-2784-513X)
- Jae Hyung Park (ORCID: https://orcid.org/0000-0002-5043-9455)
- Jeongmi Lee (ORCID: https://orcid.org/0000-0002-9948-7554)
- Yunjong Lee (ORCID: https://orcid.org/0000-0003-0182-2279)
- Seungsu Han (ORCID: https://orcid.org/0000-0002-5063-3346)
- Sanguk Son (ORCID: https://orcid.org/0009-0007-0307-4725)
- Hark Kyun Kim (ORCID: https://orcid.org/0000-0003-2755-0806)
- Jeein Lim (ORCID: https://orcid.org/0009-0004-5077-647X)
- Jongho Kim (ORCID: https://orcid.org/0009-0000-0834-5431)
- Yoonsuk Cho (ORCID: https://orcid.org/0000-0002-6549-6436)
- Jinsu Park (ORCID: https://orcid.org/0000-0002-2040-5510)
- Sang-Ho Lee (ORCID: https://orcid.org/0000-0002-6243-3245)
Institutions
- Korea Advanced Institute of Science and Technology (KR)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Journal of Extracellular Vesicles
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/jev2.70018
- Citations
- 16
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 3.74
Funders
- National Research Foundation
- National Research Foundation of Korea
- Korea Drug Development Fund
- Ministry of Education, Science and Technology
- Ministry of Science and ICT, South Korea