Hydrophobic Carbon Dots Prevent α-Synucleinopathy and Suppress Neuroinflammation to Treat Parkinson's Disease

The aggregation of α-synuclein (ɑ-syn) coupled with overexpressed neuroinflammation instigates the degeneration of dopaminergic neurons, thereby aggravating the progression of Parkinson's disease (PD). Herein, we introduced a series of hydrophobic amino acid–based carbon dots (CDs) for inhibiting ɑ-syn aggregation and mitigating the inflammation in PD neurons. Significantly, we show phenylalanine CDs (Phe-CDs) could strongly bind with ɑ-syn monomers and dimers via hydrophobic force, maintain their stability, and inhibit their further aggregates in situ and in vitro, finally conferring neuroprotection in PD by rescuing synaptic loss, ameliorating mitochondrial dysfunctions, and modulating Ca²⁺ flux. Importantly, Phe-CDs demonstrate the ability to penetrate the blood–brain barrier (BBB), significantly improving motor performance in PD mice. Our findings suggest that Phe-CDs hold great promise as a therapeutic agent for PD and the relative neurodegenerative disease.