Development of Thiolated-Graphene Quantum Dots for Regulation of ROS in macrophages

• Published in: Pharmaceutical research 2016-11, Vol.33 (11), p.2736-2747
• Main Authors: Oh, Byeongtaek, Lee, Chi H.
• Format: Article
• Language: English
• Subjects: Animals; Antilipemic agents; Apoptosis - drug effects; ATP-Binding Cassette Transporters - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cell Survival - drug effects; Citric acid; Down-Regulation; Drug Carriers; Drug delivery systems; Drug Liberation; Glutathione - metabolism; Graphene; Graphite; Graphite - chemistry; Lipids; Lipoproteins, LDL - metabolism; Low density lipoproteins; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Medical Law; Mice; Particle Size; Pharmacology; Pharmacology/Toxicology; Pharmacy; Pyrolysis; Quantum dots; Quantum Dots - chemistry; RAW 264.7 Cells; Reactive Oxygen Species - metabolism; Receptors, Scavenger - metabolism; Research Paper; Sulfhydryl Compounds - chemistry; Surface Properties
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-016-2000-7

ABSTRACT Purpose The current study was designed to develop thiolated-graphene quantum dots (SH-GQDs) as a theranostic nanocarrier and evaluate its potential for the optimal scavenging of reactive oxygen species (ROS) in macrophages. Methods SH-GQDs were prepared by hydrothermal pyrolysis of carbon source (citric acid) in the presence of reduced-glutathione (GSH). Raw264.7 cells were treated with varying concentrations of oxLDL (0.5, 1 and 2 μg/ml) in the presence or absence of SH-GQDs and cells were stained with peroxide-sensitive fluorescent dye (DCFDA). Flow cytometry analysis was performed to investigate the expression of MSR and ATP-binding cassette transporter (ABCA1) after such treatments as the negative control, oxLDL treatment and oxLDL treatment in the presence of either GQDs or SH-GQDs. Results SH-GQDs had a size ranging from 10 to 30 nm with an average size of 21.3 ± 5.2 nm. The elemental analysis indicated that SH-GQDs are mainly composed of carbon, nitrogen, oxygen and sulfur. The expression levels of ABCA1 in macrophages treated with either LDL or oxLDL were lower than those treated with the media control (the negative control: 100 ± 7.6%; LDL: 82.7 ± 1.2%; and oxLDL: 79.2 ± 1.7%). The level of ABCA1 expression increased as cells were incubated with SH-GQDs (SH-GQDs: 101.5 ± 3.1%). The level of MSR on the surface of macrophages upon being treated with SH-GQDs was lower than those with oxLDL (oxLDL: 112.1 ± 8.8% and SH-GQDs: 91.5 ± 4.2%). Conclusion The enhancement of lipid efflux and down-regulation of MSR in macrophages by SH-GQDs supported its promising usage as a theranostic nanocarrier to prevent foam cell formation and plaque development.