Carbon nanodot cellular uptake and modulation of Tumor necrosis factor-alpha-induced endothelial dysfunction

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

Abstract: In the past forty years, we have advanced our understanding of cardiovascular pathology through epidemiological and molecular studies. Atherosclerosis is one of the main cardiovascular diseases, which is also an underlying cause of more severe cardiovascular pathologies. Atherosclerosis is the chronic inflammatory response initiated by the damage to the endothelium caused by an imbalance of reactive oxygen species (ROS). This chronic inflammation causes the accumulation of plaque in arterial walls. Due to the widespread of cardiovascular disease, finding better treatment options is of importance. The interdisciplinary field of nanomedicine has been studying the application of various nanoparticles for future treatment options. A new class of nanoparticles that has promising features for medical application is carbon nanodots (CND). The citric acid-ethylenediamine synthesized CNDs used in this study have antioxidant properties making them candidates for quenching ROS and decreasing cardiovascular inflammation. Previous studies have shown that carbon nanodots have low toxicity in numerous cell lines, but CND exposure to endothelial cells has not been explored. The main goal of this study is to analyze in vitro and in vivo the effect of CNDs on endothelial dysfunction. Our in vitro results showed that the uptake of carbon nanodots by EA.hy926 endothelial cells is both time and dose-dependent. Our experiments showed cell-viability consistent with previous studies showing that nanodots have low cytotoxicity after 24 hr exposure with lower CND concentrations up to 0.3 mg/mL. However, we also found that higher concentrations affect metabolic activity via MTT assay after 6 hr exposure. CNDs significantly inhibited TNF-a-mediated expression of intracellular adhesion molecule-1 (ICAM-1), and interleukin 8, two key molecules that are responsible for the activation and the firm adhesion of monocytes to activated endothelial cells for the initiation of atherosclerosis, while the mRNA levels increased for monocyte chemoattractant protein-1 (MCP-1/CCL2). Similarly to the previously mentioned results, the gene expression of pro-inflammatory genes in cells that were treated with carbon nanodots alone showed a change in gene expression. Additional data showed that NQO1 activity is increased by nanodots after 24 hr treatment, this phase II cytoprotective enzyme is known to maintain homeostasis in the vasculature. Histology of samples from our 8-week animal study in apolipoprotein E knockout mice (Apo E -/-) suggest that plaque formation in the aorta is decreased in animals dosed with CNDs. Tissue samples from the liver of mice dosed with CNDs appear to have a decrease in hepatic lipidosis, while the kidney which is also an important detoxifying organ seems to have no significant change in histology. In conclusion, this study explored the bioapplication of carbon nanodots in endothelial cell dysfunction, and our results showed that carbon nanodots could be promising nanoparticles that may decrease cardiovascular inflammation. Future studies need to explore the role of the NF-?B pathway and the Nrf2 pathway activation to understand the underlying mode of action by which pro-inflammatory gene expression changes, and NQO1 enzymatic activity increases.

Additional Information

Language: English
Date: 2018
Apo E dificient mice, Atherosclerosis, Carbon nanodots, Carbon nanodots and atherosclerosis, Cardiovascular diseases, CND biocompatibility
Cardiovascular system $x Diseases
Biomedical materials $x Biocompatibility
Quantum dots

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