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.

项目概要/摘要这项研究的长期目标是开发碳纳米点作为新方法的基础用于治疗血管炎症及其后续疾病的“纳米药理学”。内皮功能障碍在动脉粥样硬化血管的发生、发展中发挥着重要作用作为已知的炎症生物标志物，氧化低密度脂蛋白 (OxLDL) 会诱发炎症。基因表达和单核细胞外渗导致动脉粥样硬化的发展。治疗炎症的方法对于动脉粥样硬化患者具有重要的临床意义。纳米材料对于纳米技术的发展非常重要，而碳纳米点（C-dots）是过去十年中出现的尺寸低于 10 纳米的令人着迷的新来者纳米颗粒由于其表面修饰的可变性、绿色合成方法、独特的发光特性。性能和优异的生物相容性，C-dots 引起了人们的广泛关注。活力研究表明碳点具有较低的细胞毒性，这与我们早期的研究相符。最近的研究，我们发现 C-dots 可以减少与内皮细胞中单核细胞粘附相关的 Ox-LDL 细胞，从而证明了 C 点的抗炎作用。众所周知，活性氧 (ROS) 通过使用电子顺磁性会导致内皮功能障碍。共振 (EPR) 光谱是 ROS 检测最灵敏、最特异的技术，我们的研究已还表明碳点可以直接降低体外超氧化物和羟基自由基的水平。共同表明碳点具有成为“纳米药理学”新途径的巨大潜力广泛的研究表明，可以有效治疗动脉粥样硬化等炎症性疾病。 NF-κB 的激活对于炎症反应的转录调节至关重要。沉淀碳点的抗氧化特性可以抑制 OxLDL 诱导的单核细胞粘附内皮细胞通过抑制 NF-κB 信号传导，随后调节趋化因子和该 R15 提案的具体目标是： 1a) 确定碳点是否抑制粘附分子。 OxLDL诱导的粘附分子和血管炎症标记物的表达1b)以研究是否内皮细胞中的 NF-κB 信号传导参与 C-dot 的抗炎机制；2) 开展C-dots在C57BL/6小鼠体内的生物分布和安全性研究，以及C-dots对C57BL/6小鼠的保护作用低密度脂蛋白受体 (LDLr−/−) 中的血管氧化应激、炎症和动脉粥样硬化拟议的研究还将为本科生提供宝贵的培训机会。对基础科学研究感兴趣的人预计该研究项目的完成将提供新的信息。新型碳纳米点在调节 OxLDL 介导的炎症方面的潜在应用动脉粥样硬化。

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.