Drug delivery across the blood–brain barrier (BBB) is one of the biggest challenges in modern medicine due to the BBB’s highly semipermeable property that limits most therapeutic agents of brain diseases to enter the central nervous system (CNS). In recent years, nanoparticles, especially carbon dots (CDs), exhibit many unprecedented applications for drug delivery. Several types of CDs and CD-ligand conjugates have been reported successfully penetrating the BBB, which shows a promising progress in the application of CD-based drug delivery system (DDS) for the treatment of CNS diseases. In this review, our discussion of CDs includes their classification, preparations, structures, properties, and applications for the treatment of neurodegenerative diseases, especially Alzheimer’s disease (AD) and brain tumor. Moreover, abundant functional groups on the surface, especially amine and carboxyl groups, allow CDs to conjugate with diverse drugs as versatile drug nanocarriers. In addition, structure of the BBB is briefly described, and mechanisms for transporting various molecules across the BBB and other biological barriers are elucidated. Most importantly, recent developments in drug delivery with CDs as BBB-penetrating nanodrugs and drug nanocarriers to target CNS diseases especially Alzheimer’s disease and brain tumor are summarized. Eventually, future prospects of the CD-based DDS are discussed in combination with the development of artificial intelligence and nanorobots.

The blood–brain barrier (BBB) is a major obstacle for drug delivery to the central nervous system (CNS) such that most therapeutics lack efficacy against brain tumors or neurological disorders due to their inability to cross the BBB. Therefore, developing new drug delivery platforms to facilitate drug transport to the CNS and understanding their mechanism of transport are crucial for the efficacy of therapeutics. Here, we report (i) carbon dots prepared from glucose and conjugated to fluorescein (GluCD-F) cross the BBB in zebrafish and rats without the need of an additional targeting ligand and (ii) uptake mechanism of GluCDs is glucose transporter-dependent in budding yeast. Glucose transporter-negative strain of yeast showed undetectable GluCD accumulation unlike the glucose transporter-positive yeast, suggesting glucose-transporter-dependent GluCD uptake. We tested GluCDs' ability to cross the BBB using both zebrafish and rat models. Following the injection to the heart, wild-type zebrafish showed GluCD-F accumulation in the central canal consistent with the transport of GluCD-F across the BBB. In rats, following intravenous administration, GluCD-F was observed in the CNS. GluCD-F was localized in the gray matter (e.g. ventral horn, dorsal horn, and middle grey) of the cervical spinal cord consistent with neuronal accumulation. Therefore, neuron targeting GluCDs hold tremendous potential as a drug delivery platform in neurodegenerative disease, traumatic injury, and malignancies of the CNS.

A type of orange carbon dots (O-CDs) synthesized via an ultrasonication route with citric acid and 1,2-phenylenediamine as precursors was embedded into sodium polyacrylate (SPA) as the ink for 3D printing. Characterizations of these spherical O-CDs revealed an ultra-small size (~2 nm) and excitation-independent, but solvent dependent, emission. The O-CDs were evenly distributed with low degree of aggregation in sodium polyacrylate (SPA), which was achieved due to the property that SPA can absorb water together with O-CDs. The 3D printed photoluminescent objective with the ink revealed a great potential for high yield application of these materials for additive manufacturing. This also represents the first time, bare CDs have been reported as a photoluminescent material in 3D printing, as well as the first time SPA has been reported as a material for 3D printing.

Tumor microenvironment responsive drug delivery systems are potential approaches to reduce the acute toxicity caused by high-dose cancer chemotherapy.

Elevated dopamine (DA) levels in urine denote neuroblastoma, a pediatric cancer. Saccharide-derived carbon dots (CDs) were applied to assay DA detection in simulated urine (SU) while delineating the effects of graphene defect density on electrocatalytic activity. CDs were hydrothermally synthesized to vary graphene defect densities using sucrose, raffinose, and palatinose, depositing them onto glassy carbon electrodes (GCEs). Co₃O₄ nanoparticles (NPs) were encapsulated by the CDs. Cyclic (CV) and linear sweep (LSV) voltammetry measurements were obtained, drop-casting the CDs onto GCEs and measuring DA in a phosphate-buffer solution (pH = 7). DA had an oxidation peak at +0.2 V with SucCDs, with the highest current correlating with the highest defect density. PalCD-Co₃O₄ exhibited the largest signal for DA detection in simulated urine (SU) using the oxidation peak at +0.5 V; the composite had a lower defect density compared to SucCD-Co₃O₄. The Co₃O₄-PalCDs had a DA detection range of 1 to 90 µM with an LOD of 0.88 μM in SU. SEM-EDX analysis of the electrode surface revealed semi-spherical structures with an average particle diameter of 80 ± 19 nm (n = 347) with PalCDs decorating the Co₃O₄ NPs. XRD characterization showed the incorporation of PalCD and Co₃O₄ within the composite. XPS showed electron density donation from the PalCD to Co₃O₄.