Anti-Inflammatory Effect and Cellular Uptake Mechanism of Carbon Nanodots in in Human Microvascular Endothelial Cells

Abstract

Cardiovascular disease (CVD) has become an increasingly important topic in the field of medical research due to the steadily increasing rates of mortality caused by this disease. With recent advancements in nanotechnology, a push for new, novel treatments for CVD utilizing these new materials has begun. Carbon Nanodots (CNDs), are a new form of nanoparticles that have been coveted due to the green synthesis method, biocompatibility, fluorescent capabilities and potential anti-antioxidant properties. With much research pouring into CNDs being used as bioimaging and drug delivery tools, few studies have been completed on their anti-inflammatory potential, especially in the cardiovascular system. CVD begins initially by endothelial cell inflammation. The cause of this inflammation can come from many sources; one being tumor necrosis factor (TNF-α), which can not only trigger inflammation but prolong its existence by causing a storm of pro-inflammatory cytokines. This study investigated the ability of CNDs to attenuate TNF-α induced inflammation in human microvascular endothelial cells (HMEC-1). Results show that CNDs at non-cytotoxic concentrations reduce the expression of pro-inflammatory genes, mainly Interleukin-8 (IL-8), and interleukin 1 beta (IL-1β). The uptake of CNDs by HMEC-1s was examined. Results from the studies involving channel blockers and endocytosis disruptors suggest that uptake takes place by endocytosis. These findings provide insights on the interaction CNDs and endothelial cells undergoing TNF-α induced cellular inflammation.

Carbon Nanodots Inhibit Tumor Necrosis Factor-α-Induced Endothelial Inflammation through Scavenging Hydrogen Peroxide and Upregulating Antioxidant Gene Expression in EA.hy926 Endothelial Cells

“…In this context, our results present, for the first time, direct evidence that CNDs can enter EA.hy926 endothelial cells at a concentration as low as 0.03 mg/mL. Our research group recently demonstrated that endocytosis involves CND uptake by human microvascular endothelial cells [54]. However, there may be other routes of absorption.…”

“…In the current study, EA.hy926 cells treated with CNDs for 24 h significantly increased NQO1 activity in EA.hy926 endothelial cells (Figure 6), which may be due to the longer exposure time. The possible reason why CNDs did not increase NQO1 gene expression in our previous study [54] in HMEC cells after 6 h of exposure was that the exposure time was short. It is also important to note that EA.hy926 and HMEC-1 cell lines have distinct transcriptomic profiles [86] and previous studies have suggested that these endothelial cells may have similar phenotypes but may respond differently to compounds such as the senolytic drug ABT-263 [87].…”

“…Future studies should examine SOD levels in Ea.Hy926 cells to explore the relationship between changes in SOD levels and upregulation of NQO1 enzyme content by CNDs (Figure 6). In our previous study on HMEC-1 cells [54], cells were treated with CNDs for 6 h, and a significant increase in HO-1 gene expression, but not NQO1, was detected using qPCR. In the current study, EA.hy926 cells treated with CNDs for 24 h significantly increased NQO1 activity in EA.hy926 endothelial cells (Figure 6), which may be due to the longer exposure time.…”

Carbon Dots for the Treatment of Inflammatory Diseases: An Appraisal of In Vitro and In Vivo Studies

“…TNF- α induction can increase ROS levels in endothelial cells [ 85 ]. Belperain et al reported the beneficial effects of carbon nanodots on TNF- α -induced ROS levels and inflammatory molecules in human microvascular endothelial cells [ 86 ] ( Table 1 ). Likewise, the modulating effects of cerium-doped carbon nanodots on inflammation during the course of wound healing have also been reported in a mouse model.…”

Impact of Nanomaterials in Biological Systems and Applications in Nanomedicine Field

“…In addition, the cell viability assessment confirmed the negligible toxicity of these materials in cells. An eco-friendly route was used to obtain Carbon Nanodots (CNDs), assessing their anti-inflammatory effects on Human Microvascular Endothelial Cells (HMEC-1) by Belperain et al [ 9 ]. Using non-cytotoxic concentrations (0.001, 0.03, 0.1, 0.3, 0.6, and 1.2 mg/mL), a reduction in pro-inflammatory cytokines, such as Interleukin-8 (IL-8) and Interleukin 1 beta (IL-1β) was demonstrated.…”