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

doi:10.1016/j.ijbiomac.2025.139724

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

Int J Biol Macromol. 2025 Jan 12:139724. doi: 10.1016/j.ijbiomac.2025.139724. Online ahead of print.

Authors

Chen Yang¹, Yanhao Song¹, Mingkai Luo¹, Qiuli Wang¹, Yumei Zhang¹, Juan Cen², Guanhua Du³, Jiahua Shi⁴

Affiliations

¹ Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, Henan 475004, China; State Key Laboratory of Antiviral Drugs Henan University, Henan University, Kaifeng, Henan 475004, China.
² Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, Henan 475004, China; State Key Laboratory of Antiviral Drugs Henan University, Henan University, Kaifeng, Henan 475004, China. Electronic address: cenjuan@vip.henu.edu.cn.
³ Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, Henan 475004, China; State Key Laboratory of Antiviral Drugs Henan University, Henan University, Kaifeng, Henan 475004, China. Electronic address: dugh@imm.ac.cn.
⁴ Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng, Henan 475004, China; State Key Laboratory of Antiviral Drugs Henan University, Henan University, Kaifeng, Henan 475004, China. Electronic address: sjiahua@henu.edu.cn.

PMID: 39809402
DOI: 10.1016/j.ijbiomac.2025.139724

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.

Keywords: Blood brain barrier; Exosomes; Non-motor symptoms; Parkinson's disease; Polydopamine carbon dots.