Modulation of Macrophage Polarization by Carbon Nanodots and Elucidation of Carbon Nanodot Uptake Routes in Macrophages

Abstract

Atherosclerosis represents an ever-present global concern, as it is a leading cause of cardiovascular disease and an immense public welfare issue. Macrophages play a key role in the onset of the disease state and are popular targets in vascular research and therapeutic treatment. Carbon nanodots (CNDs) represent a type of carbon-based nanomaterial and have garnered attention in recent years for potential in biomedical applications. This investigation serves as a foremost attempt at characterizing the interplay between macrophages and CNDs. We have employed THP-1 monocyte-derived macrophages as our target cell line representing primary macrophages in the human body. Our results showcase that CNDs are non-toxic at a variety of doses. THP-1 monocytes were differentiated into macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) and co-treatment with 0.1 mg/mL CNDs. This co-treatment significantly increased the expression of CD 206 and CD 68 (key receptors involved in phagocytosis) and increased the expression of CCL2 (a monocyte chemoattractant and pro-inflammatory cytokine). The phagocytic activity of THP-1 monocyte-derived macrophages co-treated with 0.1 mg/mL CNDs also showed a significant increase. Furthermore, this study also examined potential entrance routes of CNDs into macrophages. We have demonstrated an inhibition in the uptake of CNDs in macrophages treated with nocodazole (microtubule disruptor), N-phenylanthranilic acid (chloride channel blocker), and mercury chloride (aquaporin channel inhibitor). Collectively, this research provides evidence that CNDs cause functional changes in macrophages and indicates a variety of potential entrance routes.

Carbon Nanodots Attenuate Lipid Peroxidation in the LDL Receptor Knockout Mouse Brain

“…The Cary ® Eclipse™ Fluorescence Spectrophotometer was used to characterize carbon nanodots. The photoluminescent properties of carbon nanodots can be seen in their excitation wavelength around 360 nm and their emission peak around 460 nm (Figure 1), which is consistent with our previous reports [9,11].…”

“…Carbon nanodots were synthesized based on our published microwave-assisted method [9,11,12]. The samples were diluted with 10.0 mL of DDI water and then dialyzed against 5.0 L of DDI water using a 500-1000 Da MWCO (Spectra Por Float-A-Lyzer G2, 10 mL, G235063; MilliporeSigma; Darmstadt, Germany).…”

“…Not only have carbon nanodots been studied for their antioxidant and anti-inflammatory properties, but they have also become popular in research due to their excellent photoluminescence, biocompatibility, and stability [10]. Current research looking at the effects of carbon nanodots on inflammation has found that carbon nanodots reduce the expression of proinflammatory genes, act as an electron donor to support free radical scavenging, promote the phagocytic activity of macrophages, and can protect against oxidative damage from reactive oxygen species [9][10][11]. Specifically, one study looked at the effects of carbon nanodots on atherosclerosis, which corresponds with the physical state of the LDLr knockout mice used in the present study [10].…”

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

“…Carbon nanodots (CNDs) were synthesized and characterized following our published method [44,45]. Briefly, CNDs were synthesized by mixing 0.96 g of citric acid (CA) and 1 mL of Ethylenediamine (EDA) in 1 mL of deionized water.…”

Nanomaterials for Drug Delivery and Cancer Therapy

“…The second paper, by Andrew Dunphy et al, provides evidence of the interplay between macrophages and carbon nanodots, which represent a well-known target in therapeutic treatments and an important nanomaterial for biomedical applications, respectively [ 6 ]. After having found that CNDs were non-toxic in a variety of doses and that the expression of CD 206 and CD 68 could be altered by opportune treatments, they examined the potential entrance routes of CNDs into macrophages.…”