Glucose Carbon Dots Cross the Blood-Brain Barrier and Preferentially Target Spinal Neurons

The spinal cord processes and transmits neural signals controlling sensorimotor functions (e.g., breathing, locomotion, and bladder control). Disorders of the spinal cord, such as spinal cord injury and neurodegenerative diseases, often impair sensory and motor functions, causing morbidity and mortality. Therefore, it is important to develop drug delivery platforms to deliver the therapeutics directly to the spinal cord (availability) and target specific cell populations (specificity). Nanoparticles have been used as effective delivery platforms for drugs. However, whether those nanoparticles can target desired cell types in the spinal cord remains unknown. Here, we hypothesized that glucose-based carbon dots (GluCDs) cross the blood-brain barrier (BBB) and localize to neurons in the spinal cord. To test this hypothesis, we injected Sprague-Dawley rats with GluCD-fluorescein nanoconjugate intravenously. Fluorescein enabled visualization of spinal cord nanoparticle distribution and mimicked a small molecule drug cargo. Four hours post-injection, spinal cords were harvested, fixed in paraformaldehyde overnight, and cryopreserved. Tissues sections (40-μm thickness) were analyzed for cell-type colocalization with GluCD-fluorescein conjugate in the green channel and cell markers in the red channel. We used NeuN (neuronal marker), GFAP (astrocyte marker), and IBA1 (microglial marker) to label different cell types. We quantified colocalization in 3 ways: 1) Percent colocalization with different cell types, 2) 2-dimensional cross-correlation analysis with MATLAB, and 3) Positive/negative classification by 2 independent operators. Colocalization analyses demonstrated that GluCD-fluorescein nanoconjugates crossed the BBB and significantly colocalized with spinal neurons in ventral, intermediate gray, and dorsal regions. ~95% of the GluCD-fluorescein nanoparticles colocalized with neurons, and ~4% colocalized with microglia. There was no colocalization of GluCD-Fluorescein with GFAP-positive astrocytes. Thus, GluCD nanoparticles penetrate the BBB and colocalize with neurons, making them highly novel and promising neuron-specific drug delivery platforms for spinal cord injury and neurodegenerative diseases. Supported by: NIH R21NS119862-01 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.