Carbon Dots from Sugars and Ascorbic Acid: Role of the Precursors on Morphology, Properties, Toxicity, and Drug Uptake

Abstract

There is the need for reproducible, simple, high-yielding synthetic protocols aimed at obtaining carbon dots (CDs) with controlled fluorescence, photothermal and photochemical behavior, surface properties, biocompatibility, tumor targeting ability, drug absorption biodistribution, and tumor uptake. This Letter describes a systematic study on the effect of glucose, fructose, and ascorbic acid as starting materials for the preparation of highly luminescent CDs, characterized by a blue emission. Their composition and morphology are investigated by titration of OH surface groups, spectroscopic techniques, and high-resolution transmission electron microscopy (HR-TEM), and their toxicity was tested toward HeLa cells. CDs made using fructose were toxic, while those made from glucose and ascorbic acid showed good biocompatibility. The reproducible and simple synthetic procedure yields luminescent biomass-derived CDs for combined cancer therapy and diagnostics. Their doxorubicin (DOX) drug uptake was measured by spectrofluorimetry, indicating a crucial role of the morphologies of the CDs in controlling DOX loading. The glucose derived CDs showed up to 28% w/w of DOX loading.

Recent advance of carbon dots in bio-related applications

“…The blue, green, and red emissive CDs were prepared from sugar and ascorbic acid by hydrothermal reaction. DOX can also directly loaded on the surface of CDs for localized cancer therapy by simply mixing these CDs and DOX [127,128]. DOX can be released in the tumor acid microenvironment [129,130].…”

“…Typically, H 2 O 2 is produced within mitochondria and reducing species like [125]. Reprinted with permission from [128]. Copyright (2016) American Chemical Society.…”

Precursor-Dependent Photocatalytic Activity of Carbon Dots

“…HR-TEM images ( Figure 1) clearly demonstrate how the synthetic procedures affect the nanostructures: hydrothermal synthesis yielded low density and amorphous CDs, while pyrolysis rendered graphitic structures with well-defined shapes. a-Glu-CDs, a-Fru-CDs, and a-Cit-CDs were all poorly defined nanomaterials with very rarefied and irregular structures having a dimension ranging from 9 to 12 nm [2,27]. On the other hand, g-Glu-CDs and g-Cit-CDs [27] were well-dispersed nanoparticles with a quasi-spherical shape about 7-9 and 2−7 nm in size.…”

“…In this work, six different sets of CDs were synthetized using two different preparation methods-hydrothermal and pyrolytic, which yield amorphous (a-) and graphitic (g-) CDs, respectively-and three sets of reagents: citric acid (Cit-), glucose (Glu-), and fructose (Fru-) (see Supplementary Materials for full synthesis details). Briefly, a-Cit-CDs, a-Glu-CDs, and a-Fru-CDs were hydrothermally synthesized, as previously reported [2,27], from glucose, fructose, and citric acid, respectively, to yield amorphous nanomaterial composed of light molecular-like organic compounds as well as poorly-defined carbonaceous substances. Graphitic g-Glu-CDs and g-Fru-CDs were synthesized for the first time via harsh thermolysis of neat glucose or fructose, respectively, following the already published procedure optimized for citric acid derived g-Cit-CDs [27].…”

“…Fluorescent carbon dots (CDs) have drawn considerable attention in a wide range of applications ranging from the biomedical [1][2][3][4][5] to energy-related [6,7] fields. Among them, CDs appeared to be a promising luminescent bio-based nanomaterial for photocatalytic applications.…”