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Computational Analysis on Down-Regulated Images of Macrophage Scavenger Receptor

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Abstract

Background

Thiolated-graphene quantum dots (SH-GQDs) were developed and assessed for an efficient preventive means against atherosclerosis and potential toxicity through computational image analysis and animal model studies.

Experiments

Zebrafish (wild-type, wt) were used for evaluation of toxicity through the assessment of embryonic mortality, malformation and ROS generation. The amounts of SH-GQDs uptaken by mouse macrophage cells (Raw264.7) were analyzed using a flow cytometer. For the time-dependent cellular uptake study, Raw264.7 cells were treated with SH-GQDs (200 μg/ml) at specific time intervals (0.5, 1, 2, 5, 10 and 24 h). The efficacy of SH-GQDs on DiO-oxLDL efflux by Raw264.7 cells was evaluated (DiO, 3,3′-dioctadecyl-oxacarbocyanine) based on the percentage of positive cells containing DiO-oxLDL. TEER of human primary umbilical vein endothelial cells (hUVECs) were examined to assess the barrier function of the cell layers upon being treated with oxLDL.

Results

SH-GQDs significantly enhanced the efflux of oxLDL and down-regulated macrophage scavenger receptor (MSR) in Raw264.7. The ROS levels stimulated by oxidative stress were alleviated by SH-GQDs. oxLDL (10 μg/ml) significantly impaired the barrier function (TEER) of adherence junctions, which was recovered by SH-GQDs (10 μg/ml) (oxLDL: 67.2 ± 2.2 Ω-cm2 for 24 h; SH-GQDs: 114.6 ± 8.5 Ω-cm2 for 24 h). The mortality rate (46% for 1 mg/ml) of the zebra fish increased, as the concentrations and exposure duration of SH-GQDs increased. SH-GQDs exerted negligible side effects.

Conclusion

SH-GQDs have target specificity to macrophage scavenger receptor (MSR) and efficiently recovered the ROS levels and TEER. SH-GQDs did not induce endothelial cell layer disruption nor affected zebrafish larvae survival.

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Abbreviations

ABCA1:

ATP-binding cassette transporter

DCFDA:

Dichlorofluorescin diacetate

MSR:

Macrophage scavenger receptor

oxLDL:

oxidized-low density lipoprotein

ROS:

Reactive oxygen species

SH-GQDs:

Thiolated-graphene quantum dots

TEER:

Trans-epithelial Electrical Resistance

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Author information

Author notes

  1. Byeongtaek Oh

    Present address: Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, California, 94305, USA

Authors and Affiliations

  1. Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, HSB-4242, Kansas City, Missouri, 64108, USA

    Byeongtaek Oh & Chi H. Lee

  2. School of Computing and Engineering, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA

    Yugyung Lee

  3. Department of Biomedical Science and Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, 64108, USA

    Mingui Fu

Authors
  1. Byeongtaek Oh
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  2. Yugyung Lee
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  3. Mingui Fu
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  4. Chi H. Lee
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Corresponding author

Correspondence to Chi H. Lee.

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Oh, B., Lee, Y., Fu, M. et al. Computational Analysis on Down-Regulated Images of Macrophage Scavenger Receptor. Pharm Res 34, 2066–2074 (2017). https://doi.org/10.1007/s11095-017-2211-6

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  • DOI: https://doi.org/10.1007/s11095-017-2211-6

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