One-Pot Green Synthesis of Biocompatible Graphene Quantum Dots and Their Cell Uptake Studies

Abstract

Graphene-based quantum dots (GQDs) are attractive fluorophores due to their excellent photoluminescence properties, water solubility, low cost, and low toxicity. However, the lack of simple, efficient, and environmental-friendly synthesis methods often limits their biological applications. Herein, we explore a novel, one-pot, green synthesis approach for the fabrication of fluorescent GQDs without involving any harsh reagents. Graphene oxide is used as a precursor, and a 2 h hydrothermal synthesis is carried out with assistance of hydrogen peroxide; no further post purification steps are required. The effects of reaction conditions on the characteristics of GQDs are comprehensively investigated. The as-synthesized GQDs show a high photostability and excellent biocompatibility as revealed by cell viability assays for three different cell lines, namely, macrophages, endothelial cells, and a model cancer cell line. The detailed studies of cellular uptake mechanisms suggest that for all of the three cell lines the major internalization route for GQDs is caveolaemediated endocytosis followed by clathrin-mediated endocytosis at a less extent. Our results demonstrate the great potential of the as-synthesized GQDs as fluorescent nanoprobes. The study also provides unique insight into the cell−GQDs interactions, which is highly valuable for bioimaging and other related applications such as diagnostics and drug delivery.

Synthesis of graphene quantum dots and their applications in drug delivery

“…Compared with many other reported methods, it is a more green and faster method for GQDs synthesis. After that, Halder et al [46] also used GO as the precursor, oxidized and cracked it in 2 h with the help of H 2 O 2 , to obtain GQDs products, which also did not need further purification steps.…”

Green synthesis, biomedical and biotechnological applications of carbon and graphene quantum dots. A review

“…The prepared graphene quantum dots showed high photostability and significant biocompatibility as demonstrated by cell viability evaluations. These quantum dots can be applied as fluorescent nano-probes, because of the cell-graphene quantum dots interactions as they exhibited high potentials for bioimaging, diagnostics and drug delivery (Halder et al 2018).…”

“…Expectantly, increasing interest in the fabrication of these quantum dots, in view of their straightforward production and their integration with other nanomaterials, is sustainable. Although various processes and starting materials have been researched for their assembly, none or handful of these nanostructures have been able to make into marketable products yet (Liu et al 2017b;Wang et al 2016b;Murugan et al 2019;Halder et al 2018;Chen et al 2019;de Menezes et al 2019;Barras et al 2016;Nekoueian et al 2019;Li et al 2015;Mei et al 2016;Lin et al 2014).…”

“…Photoluminescence is one of the extremely attractive characteristics of carbon and graphene quantum dots, but these properties are highly dependent on the raw materials deployed in fabrication and the presence of surface functionalities on these particles which are noticeable in the case of carbon quantum dots from organic molecules and biomass. Most importantly, one of the lingering challenges has been to improve and develop the quantum yield of carbon quantum dots while taking full advantage of their intrinsic characteristics and to fine-tune their emission spectrum; the improvement in carbon quantum dots with strong fluorescence emission is crucial for biomedical imaging without harmful effects (Liu et al 2017b;Wang et al 2016b;Murugan et al 2019;Halder et al 2018;Chen et al 2019;de Menezes et al 2019;Barras et al 2016;Nekoueian et al 2019;Li et al 2015;Mei et al 2016;Lin et al 2014).…”

Do biomedical engineers dream of graphene sheets?

“…Indeed, neither the bottom-up synthesis strategies such as chemical vapor deposition nor the top-down approaches like the mechanical exfoliation of graphite and the modified Hummer's methods are currently capable of producing high-quality GBM without costly and complex manufacturing processes, low yield and toxic reagents. Therefore, the development of scalable and sustainable methodologies based on green chemistry principles 66,111,112 can be considered a major milestone to place graphene-based biomedical devices as strong candidates for real world applications and commercialization. In this context, a promising strategy was recently reported by González et al 113 , who have successfully developed a mechanochemical treatment with carbohydrates to exfoliate graphite and subsequently generate graphene in an environmentally friendly approach.…”