Carbon dots penetrating the blood-brain barrier for central nervous system nanomedicine

Central nervous system (CNS) diseases are challenging to treat because of the blood-brain barrier (BBB), formed by tight junctions that limit the transcellular transport of therapeutic drugs. Carbon dots (CDs) have emerged as versatile nanotheranostic platforms for the targeting, diagnosis, and treatment of CNS diseases owing to their ultrasmall size, intrinsic photoluminescence, tunable surface chemistry, and biocompatibility. Surface modifications of CDs with targeting ligands, polymer coatings, biomimetic membranes, and exosome-like molecules enable BBB penetration and selective brain accumulation. CDs also support multimodal imaging techniques, such as fluorescence, magnetic resonance, and photoacoustic imaging, for early disease detection and real-time therapeutic monitoring. In addition, their ability to deliver drugs, genes, and therapeutic agents, combined with their antioxidant, anti-inflammatory, photothermal, photodynamic, and sonodynamic properties, highlights their potential for the integrated diagnosis and treatment of CNS diseases. This review systematically summarizes the background of CDs, the design of BBB-penetrating CDs, and their applications in tumor diagnosis, treatment, and imaging-guided cooperative therapies for CNS diseases. Finally, current obstacles and future perspectives are discussed. This review provides a valuable reference for the rational design of BBB-penetrating CDs for the precise treatment of neurological disorders and brain cancers.