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Novel carbon nanodots for modulation of OxLDL mediated inflammation and inhibition of atherosclerosis

用于调节 OxLDL 介导的炎症和抑制动脉粥样硬化的新型碳纳米点

基本信息

批准号：
10046915
负责人：
Zhenquan Jia
金额：
$ 44.75万
依托单位：
UNIVERSITY OF NORTH CAROLINA GREENSBORO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-05 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10046915
关键词：
3-Dimensional Address Adhesions Anti-Inflammatory Agents Antiinflammatory Effect Antioxidants Atherosclerosis Attention Basic Science Binding Biodistribution Biological Markers Blood Vessels C57BL/6 Mouse Carbon Cardiovascular Diseases Cell Adhesion Molecules Cell Communication Cell Survival Characteristics Data Detection Development Disease Dose Electron Spin Resonance Spectroscopy Endothelial Cells Endothelium Extravasation Foundations Gene Expression Goals Health Care Costs Human Hydroxyl Radical In Vitro Inflammation Inflammatory Inflammatory Response Knockout Mice Low Density Lipoprotein Receptor Mediating Methods Modification Molecular Morbidity - disease rate Nanotechnology Oxidative Stress Patients Play Property Public Health Reactive Oxygen Species Research Research Project Grants Role Signal Transduction Superoxides Surface Techniques Time Toxic effect Transcriptional Activation Transcriptional Regulation United States base biomaterial compatibility chemokine clinically significant cytotoxicity effective therapy endothelial dysfunction fascinate inflammatory marker interest luminescence monocyte mortality nanodot nanomaterials nanoparticle novel novel strategies oxidized low density lipoprotein protective effect safety study training opportunity transcription factor undergraduate student uptake vascular inflammation

项目摘要

PROJECT SUMMARY/ABSTRACT The long-term goal of this research is to develop carbon nanodots as the foundation of a new approach to "nanopharmacology" for the treatment of cardiovascular diseases. Vascular inflammation and its subsequent endothelial dysfunction play an important role in the development and progression of atherosclerotic vascular disease. As a known biomarker of inflammation, oxidized low-density lipoprotein (OxLDL) induces inflammatory gene expression, and monocyte extravasation that leads to atherosclerotic development. A search for a new approach to the treatment of inflammation is of great clinical significance for patients with atherosclerosis. Nanomaterials are important to the development of nanotechnology and carbon nanodots (C-dots) are fascinating newcomers with sizes below 10 nm and have emerged in the past decade to the world of nanoparticles. Due to its variability on surface modifications, green synthesis methods, unique luminescence properties, and excellent biocompatibility, C-dots have drawn considerable attention. The results of our cell viability studies have shown that C-dots have low cytotoxicity, which complied with earlier studies. Based on our more recent studies, we found C-dots could reduce Ox-LDL that are related to monocyte adhesion in endothelial cells, thus demonstrating the anti-inflammatory effects of C-dots. On the other hand, the overproduction of reactive oxygen species (ROS) is known to cause endothelial dysfunction. By using electron paramagnetic resonance (EPR) spectroscopy, the most sensitive and specific technique for ROS detection, our studies have also showed that C-dots could directly lower the in vitro levels of superoxide and hydroxyl radicals. These results together suggest C-dots hold a great potential to become a new avenue of "nanopharmacology" for more effective treatment of inflammatory disorders such as atherosclerosis. Extensive studies demonstrated that the activation of NF-κB is essential for the transcriptional regulation of inflammatory response. We, therefore, hypothesize that the antioxidant properties of C-dots can suppress OxLDL-induced adhesion of monocytes to endothelial cells by inhibiting NF-κB signaling that subsequently regulates the expression of chemokine and adhesion molecules. The specific aims of this R15 proposal are: 1a) to determine whether C-dots inhibit the expression of OxLDL-induced adhesion molecule and vascular inflammatory markers; 1b) to investigate whether the NF-κB signaling in endothelial cells is involved in the anti-inflammatory mechanism(s) of C-dots; and 2) to carry out a bio-distribution and safety studies of C-dots in C57BL/6 mice, and the protective effects of C-dots on vascular oxidative stress, inflammation, and atherosclerosis in low–density lipoprotein receptor (LDLr−/−) knockout mice. The proposed studies will also provide valuable training opportunities for undergraduate students interested in basic science research. Fulfillment of this research project is expected to provide new information on the potential applications of novel carbon nanodots to modulate OxLDL mediated inflammation and atherosclerosis.

项目总结/文摘

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

DOI：
10.3390/nano11051116
发表时间：
2021-04-26
期刊：
Nanomaterials (Basel, Switzerland)
影响因子：
0
作者：
Dunphy A;Patel K;Belperain S;Pennington A;Chiu NHL;Yin Z;Zhu X;Priebe B;Tian S;Wei J;Yi X;Jia Z
通讯作者：
Jia Z

Carbon Nanodots Inhibit Oxidized Low Density Lipoprotein-Induced Injury and Monocyte Adhesion to Endothelial Cells Through Scavenging Reactive Oxygen Species.