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Exosomes-encapsulated biomimetic polydopamine carbon dots with dual-targeting effect alleviate motor and non-motor symptoms of Parkinson's disease via anti-neuroinflammation.

Chen Yang,Yanhao Song,Mingkai Luo,Qiuli Wang,Yumei Zhang,Juan Cen,Guanhua Du,Jiahua Shi

Published 2025 in International Journal of Biological Macromolecules

ABSTRACT

Currently, the clinical drugs for Parkinson's disease (PD) only focus on motor symptoms, while non-motor symptoms like depression are usually neglected. Even though, the efficacy of existing neurotherapeutic drugs is extremely poor which is due to the blood brain barrier (BBB). Therefore, a biomimetic polydopamine carbon dots (PDA C-dots) at 2-4 nm was synthesized, while exosomes from macrophages were applied to encapsulate PDA C-dots for improving their BBB-crossing ability and inflammation-targeting effect. Importantly, the prepared PDA C-dots@Exosomes (PEs) significantly alleviated both motor and non-motor symptoms of PD mice. Further mechanism research revealed that PEs eliminated oxidant stress and alleviated neuroinflammation to restore the injured neurons. The content of α-syn was markedly reduced, and the neural viability was dramatically improved on the areas of substantia nigra, striata, and prefrontal cortex. In summary, this work reported a mild synthetic approach to produce a kind of PDA C-dots, which had a fantastic neuroprotective effect. After being encapsulated with exosomes of macrophages, the obtained PEs could be utilized as a neuroprotective drug with great penetration ability of BBB and targeting ability into inflammatory zone. The great therapeutic effect on both motor and non-motor symptoms of PD indicates that PEs could become a promising drug for PD treatment.

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