Tryptophan carbon dots and their ability to cross the blood-brain barrier

Abstract

Drug traversal across the blood-brain barrier has come under increasing scrutiny recently, particularly concerning the treatment of sicknesses, such as brain cancer and Alzheimer's disease. Most therapies and medicines are limited due to their inability to cross this barrier, reducing treatment options for maladies affecting the brain. Carbon dots show promise as drug carriers, but they experience the same limitations regarding crossing the blood-brain barrier as many small molecules do. If carbon dots can be prepared from a precursor that can cross the blood-brain barrier, there is a chance that the remaining original precursor molecule can attach to the carbon dot surface and lead the system into the brain. Herein, tryptophan carbon dots were synthesized with the strategy of using tryptophan as an amino acid for crossing the blood-brain barrier via LAT1 transporter-mediated endocytosis. Two types of carbon dots were synthesized using tryptophan and two different nitrogen dopants: urea and 1,2-ethylenediamine. Carbon dots made using these precursors show excitation wavelength-dependent emission, low toxicity, and have been observed inside the central nervous system of zebrafish (Danio rerio). The proposed mechanism for these carbon dots abilities to cross the blood-brain barrier concerns residual tryptophan molecules which attach to the carbon dots surface, enabling them to be recognized by the LAT1 transporter. The role of carbon dots for transport open promising avenues for drug delivery and imaging in the brain.

Keywords: Blood-brain barrier; Carbon dots; Drug delivery; Zebrafish.

Figure 1:

(a) Absorption and normalized photoluminescence spectra of CD-EDA. (b) Photoluminescence spectrum of CD-EDA. (c) Absorption and normalized photoluminescence spectra of CD-Urea. (d) Photoluminescence spectrum of CD-Urea. Optical pathlength, 1 cm. Solvent, water.

Figure 2:

(a) AFM image of CD-EDA. (b) AFM height profile of CD-EDA. (c) TEM image and histogram of CD-EDA. Scale bar is 10 nm. (d) AFM image of CD-Urea. (e) AFM height profile of CD-Urea. (f) TEM image and histogram of CD-Urea. Scale bar in TEM images is 10 nm.

Figure 3:

Confocal microscopic images of a six-day-old, transgenic zebrafish larva expressing mcherry (585 nm) in the central nervous system. The larvae were injected with either 10,000 MW fluorescein dextran dye (496 nm) alone (control, top row), or a combination of dye and CD-EDA (second row) or a combination of dye and CD-Urea (third row). Fluorescence from CDs (405 nm) that cross the blood brain barrier can be seen in the central canal that is highlighted with the red arrows.