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

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 caveolae-mediated 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.

[1]  Yan Li,et al.  Free-Radical-Assisted Rapid Synthesis of Graphene Quantum Dots and Their Oxidizability Studies. , 2016, Langmuir : the ACS journal of surfaces and colloids.

[2]  Jingyan Zhang,et al.  Effect of Lateral Size of Graphene Quantum Dots on Their Properties and Application. , 2016, ACS applied materials & interfaces.

[3]  Chengyi Hou,et al.  Graphene directed architecture of fine engineered nanostructures with electrochemical applications , 2017 .

[4]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[5]  Qijin Chi,et al.  Electroactive and biocompatible functionalization of graphene for the development of biosensing platforms. , 2017, Biosensors & bioelectronics.

[6]  Hyoyoung Lee,et al.  An Electrolyte‐Free Flexible Electrochromic Device Using Electrostatically Strong Graphene Quantum Dot–Viologen Nanocomposites , 2014, Advanced materials.

[7]  Dustin K. James,et al.  Graphene Chemistry: Synthesis and Manipulation , 2011 .

[8]  Hong Zhang,et al.  Synthesis of Luminescent Graphene Quantum Dots with High Quantum Yield and Their Toxicity Study , 2015, PloS one.

[9]  Ying Fu,et al.  Facile synthesis of water-soluble, highly fluorescent graphene quantum dots as a robust biological label for stem cells , 2012 .

[10]  Richard A. Revia,et al.  Paramagnetic Properties of Metal‐Free Boron‐Doped Graphene Quantum Dots and Their Application for Safe Magnetic Resonance Imaging , 2017, Advanced materials.

[11]  Qixing Zhou,et al.  Graphene Oxide Quantum Dots Reduce Oxidative Stress and Inhibit Neurotoxicity In Vitro and In Vivo through Catalase‐Like Activity and Metabolic Regulation , 2018, Advanced science.

[12]  William G Telford,et al.  Dynamics and mechanisms of quantum dot nanoparticle cellular uptake , 2010, Journal of Nanobiotechnology.

[13]  Chengyi Hou,et al.  Ultralight, Flexible, and Semi-Transparent Metal Oxide Papers for Photoelectrochemical Water Splitting. , 2017, ACS applied materials & interfaces.

[14]  W. Smith,et al.  Structure and Properties of Carbon Black - Changes Induced by Heat Treatment , 1953 .

[15]  Shan Sun,et al.  A facile and high-efficient approach to yellow emissive graphene quantum dots from graphene oxide , 2017 .

[16]  Qiangbin Wang,et al.  Enhanced Nanodrug Delivery to Solid Tumors Based on a Tumor Vasculature‐Targeted Strategy , 2016 .

[17]  N. Wu,et al.  Fluorescence and Sensing Applications of Graphene Oxide and Graphene Quantum Dots: A Review. , 2017, Chemistry, an Asian journal.

[18]  Jingyan Zhang,et al.  Photo-Fenton reaction of graphene oxide: a new strategy to prepare graphene quantum dots for DNA cleavage. , 2012, ACS nano.

[19]  R. Asahi,et al.  Optically Tunable Amino‐Functionalized Graphene Quantum Dots , 2012, Advanced materials.

[20]  T. Nann,et al.  Graphene Quantum Dots , 2014 .

[21]  Warren C W Chan,et al.  Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. , 2007, Nano letters.

[22]  Yunchao Li,et al.  Surrounding media sensitive photoluminescence of boron-doped graphene quantum dots for highly fluorescent dyed crystals, chemical sensing and bioimaging , 2014 .

[23]  Chunru Wang,et al.  Eco-friendly synthesis of size-controllable amine-functionalized graphene quantum dots with antimycoplasma properties. , 2013, Nanoscale.

[24]  Huan He,et al.  Red, Yellow, and Blue Luminescence by Graphene Quantum Dots: Syntheses, Mechanism, and Cellular Imaging. , 2017, ACS applied materials & interfaces.

[25]  Minghong Wu,et al.  Hydrothermal Route for Cutting Graphene Sheets into Blue‐Luminescent Graphene Quantum Dots , 2010, Advanced materials.

[26]  B. K. Gupta,et al.  Graphene quantum dots derived from carbon fibers. , 2012, Nano letters.

[27]  J. Donaldson,et al.  Search for inhibitors of endocytosis , 2012, Cellular logistics.

[28]  G. Lalwani,et al.  Degradation of Graphene by Hydrogen Peroxide , 2014 .

[29]  N. Voelcker,et al.  Rhodamine-Functionalized Graphene Quantum Dots for Detection of Fe(3+) in Cancer Stem Cells. , 2015, ACS applied materials & interfaces.

[30]  X. Qu,et al.  Specific Oxygenated Groups Enriched Graphene Quantum Dots as Highly Efficient Enzyme Mimics. , 2018, Small.