Modulation of macrophage polarization by carbon nanodots
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Andrew M. Dunphy (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- Zhenquan Jia
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. Free oxygen radicals modify low-densitiy lipoprotieins (LDL) into ox-LDL. Upon injury to the endothelium of blood vessels by ox- LDL, circulating monocytes differentiate into pro-inflammatory (M1) or anti-inflammatory (M2) macrophages. In progressing lesions, M1 macrophages engulf excess ox-LDL. In the process, these macrophages become lipid-laden and lose mobility, finally proceeding to settle en-masse on the bed of arteries as plaque. Dysregulated plaque build-up in arteries results in a several fatal long-term health issues. Due to their crucial role as mediators in atherogenesis, as well as their involvement in several aspects of the immune response, macrophages 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. CNDs have various attractive qualities that have made them useful for several applications, including biosensing and drug delivery. A key feature of CNDs is their capability for free radical scavenging ability. However, no reports exist analyzing the interaction of CNDs and macrophages. 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-treated 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 reduced 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, our project aimed at determining potential entrance and exit 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). Lastly, our data denotes a significant increase in the release of CNDs when macrophages were also treated with nocodazole. Collectively, this research provides evidence that CNDs cause functional changes in macrophages, and indicates a variety of potential entrance and exit routes.
Modulation of macrophage polarization by carbon nanodots
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Created on 5/1/2020
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Additional Information
- Publication
- Thesis
- Language: English
- Date: 2020
- Keywords
- Carbon Nanodots, Chemical Inhibitors, M1/M2 Biomarkers, Macrophage Polarization, Phagocytic Activity, Trypan Blue
- Subjects
- Macrophages
- Chemical inhibitors
- Nanostructured materials
- Atherosclerosis $x Treatment
- Trypan blue