Carbon quantum dots exacerbate Parkinson's disease-like pathology through microglia-mediated neuroinflammatory responses with toxicological implications.

The global burden of Parkinson's disease (PD) is projected to double by 2050, with early-onset cases demonstrating accelerated progression and limited therapeutic options. Recently, carbon quantum dots (CQDs) emerge as promising nanoplatforms for PD theragnostic, but their paradoxical role in exacerbating neuroinflammation and neurodegeneration shows the urgent need for mechanistic safety evaluations to bridge their therapeutic potential and neurotoxic risks. This study conducted a neuro-safety assessment of CQDs based on MPP+-induced mice and cell PD models to stimulate the theragnostic scenarios of CQDs in PD patients in the real-world. The results showed that CQDs not only promoted the onset and progression of PD-like damages in mice and cells but also exacerbated PD-related neurological dysfunction and structural damages in PD models. The microglia-mediated neuroinflammatory reactions were identified to be pivotal mediators of CQDs exacerbating PD-like damages based on machine learning (ML) approaches. According to these key toxic targets, we established molecular docking technology and network pharmacology to propose interventional strategies, including functional modification of CQDs and anti-neuroinflammatory drugs to alleviate the exacerbation of PD-like damages induced by CQDs, thereby ensuring the safe application of CQDs in the diagnosis and treatment of PD.