Hydrothermal synthesis of nitrogen-doped carbon dots with real-time live-cell imaging and blood–brain barrier penetration capabilities

Abstract

Nitrogen-doped carbon dots (N-CDs) were synthesized using a one-pot hydrothermal treatment with citric acid in the presence of polyethylenimine. Transmission electron microscopy analysis revealed that the N-CDs were monodispersed and quasi-spherical with an average size of ~2.6 nm. Under ultraviolet irradiation the N-CDs emitted a strong blue luminescence with a quantum yield as high as 51%. Moreover, the N-CDs exhibited a negligible cytotoxicity and could be applied as efficient nanoprobes for real-time imaging of live cells. In addition, the ability of the N-CDs to cross the blood–brain barrier (BBB) in a concentration-dependent manner was demonstrated using an in vitro BBB model. Therefore, these PEI-passivated N-CDs with real-time live-cell imaging and BBB-penetration capabilities hold promise for traceable drug delivery to the brain.

Keywords:

• hydrothermal synthesis
• nitrogen-doped carbon dots
• bioimaging

Supplementary materials

Video S1 N-CDs as optical nanoprobes for in vitro real-time live-cell imaging.

Abbreviation: N-CDs, nitrogen-doped carbon dots.

Figure S1 QY measurement of N-CDs using quinine sulfate as the reference.

Abbreviations: Abs, absorbance; au, arbitrary units; N-CDs, nitrogen-doped carbon dots; PL, photoluminescence; QY, quantum yield.

Figure S2 PL intensity of N-CDs against excitation time (λ_ex =360 nm).

Abbreviations: au, arbitrary units; N-CDs, nitrogen-doped carbon dots; PL, photoluminescence.

Figure S3 FL intensity forms real-time cell imaging of N-CDs for 12 h with a 30-min interval.

Abbreviations: au, arbitrary units; FL, fluorescence; N-CDs, nitrogen-doped carbon dots.

Figure S4 Confocal laser scanning microscopy images of 293T cells incubated with N-CDs at different dosages (0, 2, and 4 mg/mL).

Abbreviation: N-CDs, nitrogen-doped carbon dots.

Figure S5 TEER values of rat brain endothelial cell monolayers in monoculture and coculture with astrocytes for 10 days in transwells after coated with poly-l-lysine.

Note: All data are expressed as mean ± SD (n=3–4).

Abbreviations: SD, standard deviation; TEER, transendothelial electrical resistance.

Acknowledgments

The authors gratefully acknowledge financial support from the National Foundation of Natural Sciences of China (81173121 and 81573683), Beijing Natural Science Foundation (7162023), and Beijing Laboratory for Biomedical Detection Technology and Instrument (PXM2014-014226-000021) under the jurisdiction of the Beijing Municipality of China, Central Public-interest Scientific Institution Basal Research Fund (2015 CZ-29).

Disclosure

The authors report no conflicts of interest in this work.