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

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.