Crossing Blood‐Brain Barrier with Carbon Quantum Dots

Abstract

The blood‐brain barrier (BBB) is a semi‐permeable structure, which is essential for the protection of the central nervous system (CNS). BBB selectively allows the passage of the necessary small molecules/nutrients from the blood to the brain while blocking pathogens or toxins. However, BBB becomes a major obstacle during disease since it significantly hinders the drug delivery to the CNS. Therefore, developing a drug delivery system to cross BBB is highly desired. Recently, nanoparticles (NPs) have become emergent tools to assist drugs to cross BBB. Since most NPs cannot cross BBB by themselves, the nanoparticle‐mediated drug delivery heavily depends on conjugating the NPs to the ligands such as transferrin to pass through the BBB via receptor‐mediated endocytosis.Here, we designed Carbon quantum dots (CDs) that can cross BBB without the need of a ligand. We hypothesized that the saccharide‐based CDs will have an amphiphilic structure with surface groups that resemble the saccharide precursor. Therefore, these CDs will be able to cross BBB either with the aid of glucose transporter proteins or by passive diffusion.CDs were prepared via a bottom‐up approach using hydrothermal carbonization of saccharides and characterized using various spectroscopic, microscopic and surface chemistry methods such as UV/vis, fluorescence, FTIR/ATR, TEM, AFM and Langmuir monolayers. To test our hypothesis, CDs were injected into the heart of wild‐type zebrafish, Danio rerio. The confocal images showed the accumulation of CDs in the CNS of zebrafish confirming the ability to cross BBB. CDs were also shown to pass through rat BBB 45 min after intravenous tail injection (2.5 mg/kg). Following transcardial perfusion, rat spinal cord is post‐fixed in paraformaldehyde overnight and cryoprotected in sucrose. Presence of CDs in the CNS was confirmed in 40 μm tissue sections via epifluorescence microscopy. These proof‐of‐principle studies suggest that saccharide‐based CDs can cross BBB in different vertebrate species. Further studies should address if the amount of BBB penetration is sufficient to cause a biologically meaningful effect in the CNS.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.