Near‐infrared emission Cu, N‐doped carbon dots for human umbilical vein endothelial cell labeling and their biocompatibility in vitro

Abstract

Quantum dots (QDs) are luminescent semiconductor nanomaterials (NMs) with various biomedical applications, but the high toxicity associated with traditional QDs, such as Cd‐based QDs, limits their uses in biomedicine. As such, the development of biocompatible metal‐free QDs has gained extensive research interests. In this study, we synthesized near‐infrared emission Cu, N‐doped carbon dots (CDs) with optimal emission at 640 nm and a fluorescence quantum yield of 27.1% (in N,N‐dimethylformamide [DMF]) by solvothermal method using o‐phenylenediamine and copper acetate monohydrate. We thoroughly characterized the CDs and showed that they were highly fluorescent and stable under different conditions, although in highly acidic (pH = 1–2) or alkaline (pH = 12–13) solutions, a redshift or blueshift of fluorescence emission peak of Cu, N‐doped CDs was also observed. When exposed to human umbilical vein endothelial cells (HUVECs), Cu, N‐doped CDs only significantly induced cytotoxicity at very high concentrations (100 or 200 μg/ml), but their cytotoxicity appeared to be comparable with carbon black (CB) nanoparticles (NPs) at the same mass concentrations. As the mechanisms, 200 μg/ml Cu, N‐doped CDs and CB NPs promoted endoplasmic reticulum (ER) stress proteins IRE1α and chop, leading to increased cleaved caspase 3/pro‐caspase 3 ratio, but CB NPs were more effective. At noncytotoxic concentration (50 μg/ml), Cu, N‐doped CDs successfully labeled HUVECs. In summary, we successfully prepared highly fluorescent and relatively biocompatible CDs to label HUVECs in vitro.

Carbon Dots in Biomedicine: A Review

“…54,59,62,63 CDs, as a new type of carbon material, are widely used in the fields of optoelectronic devices, photocatalysis, and biomedicine due to their good properties. 27,45 Recently, various unusual absorption characteristics of CDs have been reported. Okuyama et al developed yellow fluorescent CDs with a large amount of pyrrole nitrogen on the surface through a one-step hydrothermal method, which is shown in Figure 3a,b.…”

“…Gold nanoclusters and silica nanoparticles have good light stability and biocompatibility, but they exhibit a low fluorescence quantum yield, poor biodegradation, and a high price . By contrast, carbon dots (CDs) show excellent biocompatibility and good optical properties, indicating their potential in imaging and cancer treatment applications. , Compared with other materials, CDs, due to their unique optical properties, high stability, good biocompatibility, and water solubility, can be used as multifunctional nanoplatforms with potential applications in fluorescence imaging and photodynamic and photothermal therapy. − In addition, the doping of Se, Cu, Hf, and other heteroatoms makes the material have a higher versatility and better performance . For example, Wang et al synthesized a new type of copper-doped CDs through the coordination between a carboxyl group and Cu 2+ , using a poly­(copper acrylate) complex as a material by a high-temperature heating method.…”

“…25 By contrast, carbon dots (CDs) show excellent biocompatibility and good optical properties, indicating their potential in imaging and cancer treatment applications. 26,27 Compared with other materials, CDs, due to their unique optical properties, high stability, good biocompatibility, and water solubility, can be used as multifunctional nanoplatforms with potential applications in fluorescence imaging and photodynamic and photothermal therapy. 27−33 In addition, the doping of Se, Cu, Hf, and other heteroatoms makes the material have a higher versatility and better performance.…”

Synthesis of Highly Near-Infrared Fluorescent Graphene Quantum Dots Using Biomass-Derived Materials for In Vitro Cell Imaging and Metal Ion Detection

“…24 Although there have been recent reports of NIR-containing GQDs 25 and carbon dots, 26 there remain several undesirable traits during synthesis procedures such as the use of strong acids, 27 element doping, 28,29 lengthy reactions, 30 and forms of graphene oxide. 31 Additionally, many synthesized GQDs with NIR fluorescence usually contain their peak in the lower NIR region 24,32,33 (650−810 nm) or are dependent on larger GQD particle size. 34 NIR fluorescent materials for bioimaging are sought after due to their deep tissue penetration, weak emission light scattering, and lower background which helps improve signal-to-noise ratios.…”

“…Although there have been recent reports of NIR-containing GQDs and carbon dots, there remain several undesirable traits during synthesis procedures such as the use of strong acids, element doping, , lengthy reactions, and forms of graphene oxide . Additionally, many synthesized GQDs with NIR fluorescence usually contain their peak in the lower NIR region ,, (650–810 nm) or are dependent on larger GQD particle size . NIR fluorescent materials for bioimaging are sought after due to their deep tissue penetration, weak emission light scattering, and lower background which helps improve signal-to-noise ratios. ,, Having a carbon-based nanomaterial that emits fluorescence in the NIR region would provide not only the above-listed imaging benefits but also reduced toxicity and easier cellular uptake and integration because of their chemical make-up and small particle size.…”