Novel Carbon Nanodots against Vascular Inflammation

抗血管炎症的新型碳纳米点

• 批准号: 9171173
• 负责人: Zhenquan Jia
• 金额: $ 45.52万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-20 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9171173
• 关键词: Adhesions; Adverse effects; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Apolipoprotein E; Atherosclerosis; Attention; Basic Science; Binding; Blood; Blood Vessels; CCL2 gene; Carbon; Cell Adhesion; Cell Adhesion Molecules; Clinical; Data; Development; Disease; Endothelial Cells; Family; Goals; Health Care Costs; Human; IL8 gene; Inflammation; Inflammatory; Inflammatory Response; Modification; Molecular; Mononuclear; Morbidity - disease rate; Mus; NF-kappa B; Nanotechnology; Nuclear; Nuclear Translocation; Optical Methods; Oxidative Stress; Pathogenesis; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Play; Production; Property; Reactive Oxygen Species; Research; Research Project Grants; Role; Signal Transduction; Steroids; Surface; TNF gene; TNFRSF5 gene; Time; Toxic effect; Transcriptional Regulation; Umbilical vein; United States; Vascular Diseases; base; chemokine; cytokine; effective therapy; endothelial dysfunction; fascinate; graduate student; interest; manufacturing process; monocyte; mortality; nanomaterials; nanoparticle; novel; p65; protective effect; training opportunity; transcription factor; undergraduate student; vascular inflammation

PROJECT SUMMARY/ABSTRACT The long-range goal of this research is to development novel carbon nanodots as a new avenue of "nanopharmacology" for treatment of vascular diseases. Vascular inflammation and its subsequent endothelial dysfunction play a fundamental role in the initiation and progression of atherosclerotic vascular disease. It is believed that tumor necrosis factor (TNF)-alpha is critically involved in the pathogenesis of atherosclerosis. Carbon nanodots (C-dots) are fascinating newcomers to the world of nanoparticles with sizes below 10 nm. C-dots have drawn considerable attentions and become a rising star in the nanocarbon family due to their lower toxicity, versatile surface modification, green synthetic method, optical stability, and good bio-compatibility. Our recent preliminary data for the first time showed that C-dots significantly reduced TNF-alpha-induced adhesion of monocytes to human primary umbilical vein endothelial cells (HUVECs) suggesting a potential anti-inflammatory action of C-dots against vascular dysfunction. Overproduction of reactive oxygen species (ROS) is known to cause endothelial dysfunction. Our preliminary data further showed that C-dots decreased ROS production and the treatment is nontoxic. These results suggest 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 IL-8 and MCP-1. Our preliminary data further showed that TNF-alpha significantly increased NF-κB binding activity indicating that activation of the transcription factor NF-κB might be critical for the TNF-alpha-induced inflammatory response. Based on these data, we therefore hypothesize that C-dots with respect to antioxidant properties suppress TNF-alpha-induced adhesion of monocytes to endothelial cells via inhibition of NF-κB signaling that subsequently regulates chemokine and adhesion molecular expression. Thus, the specific aims of this R15 proposal are: 1): to determine whether carbon nanodots inhibit TNF-alpha-induced expression of adhesion molecules, markers of vascular inflammation and nuclear translocation of NF-κB, and whether the mechanism is through NF-κB signaling in HUVECs; 2) to carry out the Bio-distribution, safe studies of carbon nanodots and the protective effects of carbon nanodots on vascular oxidative stress, inflammation and atherosclerosis in Apo E-/- mice. Based on our pilot studies, we believe that C-dots may provide a new avenue of "nanopharmacology" for more effective treatment of inflammatory disorders such as atherosclerosis and the proposed studies will also provide valuable training opportunities to undergraduate and graduate students interested in basic science research. Fulfillment of this research project is expected to provide new information on the potential application of novel carbon nanodots to the treatment of vascular diseases.

项目总结/摘要 这项研究的长期目标是开发新的碳纳米点作为一种新的途径， 用于治疗血管疾病的“纳米药理学”。血管炎症及其后续 内皮功能障碍在动脉粥样硬化的发生和发展中起着重要作用， 疾病据信，肿瘤坏死因子（TNF）-α与肿瘤坏死因子（TNF）-α的发病机制密切相关。 动脉粥样硬化碳纳米点（C-dots）是纳米颗粒世界的迷人新人， 尺寸小于10 nm。碳点是纳米碳材料中的一颗冉冉升起的星星，引起了人们的广泛关注 由于它们的低毒性、多用途的表面改性、绿色合成方法、光学稳定性， 生物相容性好。我们最近的初步数据首次表明，C点显着减少 TNF-α诱导的单核细胞与人原代脐静脉内皮细胞（HUVECs）的粘附 表明C点对血管功能障碍具有潜在的抗炎作用。生产过剩 已知活性氧（ROS）引起内皮功能障碍。我们的初步数据进一步 表明C-dots减少了ROS的产生，并且处理是无毒的。这些结果表明， “纳米药理学”的途径，用于更有效地治疗炎症性疾病， 动脉粥样硬化大量的研究表明，NF-κB的活化是细胞凋亡的关键。 IL-8和MCP-1的转录调节。我们的初步数据进一步表明， 显著增加NF-κB结合活性，表明转录因子NF-κB活化 可能对TNF-α诱导的炎症反应至关重要。根据这些数据，我们 假设C-点抗氧化特性抑制TNF-α诱导粘附， 通过抑制NF-κB信号传导，随后调节趋化因子， 粘附分子表达因此，这一R15提案的具体目标是： 碳纳米点抑制TNF-α诱导的粘附分子表达，血管内皮细胞标志物 炎症和NF-κB的核转位，以及其机制是否通过NF-κB信号转导， 2）开展碳纳米点的生物分布、安全性研究及对HUVECs的保护作用 碳纳米点对Apo E-/-小鼠血管氧化应激、炎症和动脉粥样硬化的影响。基于 我们的试点研究，我们相信，C点可能会提供一个新的途径“纳米药理学”，为更多的 有效治疗炎性疾病如动脉粥样硬化，并且所提出的研究还将 为对基础科学感兴趣的本科生和研究生提供宝贵的培训机会 research.该研究项目的完成有望提供有关潜在的新信息， 新型碳纳米点在治疗血管疾病中的应用。

项目成果

Antioxidant Capacity of Nitrogen and Sulfur Codoped Carbon Nanodots.

• DOI: 10.1021/acsanm.8b00404
• 发表时间: 2018-05
• 期刊: ACS applied nano materials
• 影响因子: 5.9
• 作者: Wendi Zhang;J. Chavez;Z. Zeng;B. Bloom;Alex T. Sheardy;Zuowei Ji;Ziyu Yin;D. Waldeck;Z. Jia-Z.-J

GPx4 in Bacterial Infection and Polymicrobial Sepsis: Involvement of Ferroptosis and Pyroptosis.

• DOI: 10.20455/ros.2019.835
• 发表时间: 2019-05-01
• 期刊: Reactive oxygen species (Apex, N.C.)
• 作者: Zhu, Hong;Santo, Arben;Robert Li, Y
• 通讯作者: Robert Li, Y

Nanospray desorption electrospray ionization mass spectrometry of untreated and treated probiotic Lactobacillus reuteri cells.

• DOI: 10.1007/s00216-018-1071-1
• 发表时间: 2018-07
• 期刊: Analytical and bioanalytical chemistry
• 影响因子: 4.3
• 作者: Uwakweh AO;Mwangi JN;Todd D;Jia Z;Chiu NHL
• 通讯作者: Chiu NHL

A fluorescence-electrochemical study of carbon nanodots (CNDs) in bio- and photoelectronic applications and energy gap investigation.

• DOI: 10.1039/c7cp02875j
• 发表时间: 2017-08-02
• 期刊: Physical chemistry chemical physics : PCCP
• 作者: Zeng Z;Zhang W;Arvapalli DM;Bloom B;Sheardy A;Mabe T;Liu Y;Ji Z;Chevva H;Waldeck DH;Wei J
• 通讯作者: Wei J

Carbon Nanodots Derived from Urea and Citric Acid in Living Cells: Cellular Uptake and Antioxidation Effect

• DOI: 10.1021/acs.langmuir.0c01598
• 发表时间: 2020-07-28
• 期刊: LANGMUIR
• 影响因子: 3.9
• 作者: Ji, Zuowei;Yin, Ziyu;Wei, Jianjun
• 通讯作者: Wei, Jianjun