Natural Product-Derived Carbon Dots in Neurodegenerative Diseases: Advances in Blood-Brain-Barrier-Related Delivery, Neuroprotection, and Theranostics.

The mechanisms underlying neurodegenerative diseases (NDDs) involve multiple pathological processes, such as abnormal protein aggregation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and the disruption of neurovascular unit homeostasis. The blood-brain barrier (BBB) restricts drug exposure in the brain, posing a significant challenge for central nervous system delivery and for improving therapeutic efficacy. In recent years, carbon dots derived from natural products (CDs) have emerged as candidate materials for brain delivery and theranostic applications due to their small size, modifiable surfaces, fluorescence-tracking capability, and potential neuroprotective activity. This narrative review summarizes their sources, physicochemical characteristics, biological basis, interactions with the BBB, delivery strategies, neuroprotective effects, and imaging applications. Current evidence suggests that these CDs can alleviate oxidative stress and inflammatory responses, influence abnormal protein aggregation, and support drug delivery and fluorescence tracking in certain cellular and animal models. However, BBB permeability, brain fluorescence signals, brain parenchymal exposure, and therapeutic efficacy represent distinct levels of evidence and should not be considered interchangeable. Future studies should focus on strengthening material standardization, ensuring batch-to-batch consistency, characterizing absorption, distribution, metabolism, and excretion (ADME), conducting long-term safety assessments, and validating using humanized BBB models.