Carbon nanodot uptake and their effects on macrophages upon challenge with oxidized LDL and TNF-alpha

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Lena M. Smith (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Zhenquan Jia

Abstract: Atherosclerosis, a leading cause of cardiovascular disease worldwide, represents a global concern because of its large economic and public welfare burden. Macrophages play important physiological and pathological roles in the development of atherosclerosis. Carbon nanodots (CNDs), members of a new class of carbon-based nanoparticles, serve as novel candidates for biomedical applications including bioimaging, biosensing, drug delivery, and especially modulation of cardiovascular inflammation because of their fluorescence, stability, and antioxidant properties. However, the action of CNDs on the macrophages has not yet been explored. Tumor Necrosis Factor a (TNF-a) and oxidized low-density lipoprotein (oxLDL) are important mediators for the alteration of the expression of genes involved in inflammation-mediated atherosclerosis. OxLDL is internalized by macrophages, increasing secretion of proinflammatory cytokines and inducing foam cells formation as lipid accumulates. In this study, the effects of CNDs on TNF-a and oxLDL induced inflammation in macrophages were examined. Our results demonstrate that CNDs have low toxicity and display dose- and time dependent uptake within THP-1 human monocyte-derived macrophages; human monocytic cell lines were differentiated into macrophages by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. Cotreatment with CNDs significantly reduced gene expression of the cytokine interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1)/CCL2, and interleukin-1ß (IL-1ß) in the context of both TNF-a and oxLDL mediated inflammation. Cotreatment with CNDs also reduced TNF-a mediated vascular cell adhesion protein 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM) gene expression, and oxLDL mediated TNF-a expression. This demonstrates the anti-inflammatory effects of CNDs. While internalization of oxLDL induces foam cell formation, CNDs ameliorated lipid uptake. Furthermore, CNDs reduced oxLDL induced cytotoxicity in THP-1 human monocyte-derived macrophages. Gene expression of Gamma-glutamate Cystine Ligase Catalytic Subunit (GCLc) and NADPH quinone dehydrogenase (NQO1), enzymes involved in reactive oxygen species (ROS) detoxification, was not altered by CNDs. However, NF-?B transcriptional activity, mediated by TNF-a and oxLDL, was decreased by CNDs treatment in macrophages. Collectively, this research provides evidence for the ability of CNDs to attenuate TNF-a and oxLDL induced inflammation in macrophages. [This abstract has been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]

Additional Information

Language: English
Date: 2019
Carbon nanodots, Inflammation, Macrophages, Oxidized LDL
Nanostructured materials
Low density lipoproteins
Tumor necrosis factor

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