Green Tea Nanocarriers: A Promising Approach for the Prevention and Treatment of

绿茶纳米载体：一种有前途的预防和治疗方法

• 批准号: 8232871
• 负责人: Shu Wang
• 金额: $ 31.4万
• 依托单位: TEXAS TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8232871
• 关键词: Achievement; Adverse effects; Affinity; Aorta; Arterial Fatty Streak; Atherogenic Diet; Atherosclerosis; Binding; Biocompatible; Biological Availability; Blood; Blood Circulation; CD36 gene; Cause of Death; Cells; Cellular Assay; Chitosan; Cholesterol; Chronic Disease; Deposition; Developed Countries; Development; Diagnosis; Disease; Dose; Drug Delivery Systems; Encapsulated; Engineering; Enzyme-Linked Immunosorbent Assay; Epigallocatechin Gallate; Foam Cells; Goals; Green tea; Health Sciences; High Pressure Liquid Chromatography; Human; Immunohistochemistry; In Vitro; Inflammatory; Knockout Mice; Knowledge; Lesion; Ligands; Lipids; Low Density Lipoprotein Receptor; Low-Density Lipoproteins; Marketing; Measures; Mediating; Medical Care Costs; Membrane; Methods; Modification; Mus; Nutraceutical; Nutrient; Organ; Outcome; Pathologist; Peritoneal Macrophages; Plasma; Prevention; Prevention approach; Prevention therapy; Production; Quality of life; Research; Safety; Savings; Solubility; Specificity; Surface; System; Techniques; Therapeutic; Time; Tissues; Toxic effect; United States; Work; disability; disorder prevention; feeding; fluorescence microscope; immunogenicity; improved; in vivo; innovation; insight; interest; macrophage; macrophage scavenger receptors; monocyte; nanocarrier; nanoparticle; nanostructured; oxidized low density lipoprotein; prevent; receptor; release factor; scavenger receptor; uptake

DESCRIPTION (provided by applicant): Atherosclerotic cardiovascular disease is the most common cause of death in the United States. Many natural compounds show promise to remedy this serious illness, but their low level of bioavailability and target specificity in the bdy makes administering them in therapeutic doses unrealistic. This is particularly true for (-)- epigallocatechin gallate (EGCG), a natural compound found in green tea, that is valuable for the prevention and treatment of atherosclerosis. The purpose of this project is to synthesize EGCG encapsulated chitosan-coated nanostructured lipid carriers (CSNLC-EGCG) to increase its level of stability, cellular bioavailability and targeting to aortic intimal macrophages, with the goal o preventing and reversing atherosclerotic lesion development. Aortic intimal macrophages are major cells responsible for atherosclerotic lesion development. These macrophages take up cholesterol-rich low- density lipoprotein (LDL), leading to the formation of cholesterol-laden macrophages (foam cells), which characterize early atherosclerotic lesions. EGCG can decrease cholesterol accumulation in aortic macrophages, inhibit foam cell formation, and reduce inflammatory factor release from aortic macrophages. These actions inhibit atherosclerotic lesion development and may promote regression of atherosclerotic lesions. Low levels of EGCG stability, bioavailability, and target specificity prevent these benefits from being fully realized. There is a critical need for engineered EGCG carriers to enhance its stability, cellular bioavailability and target specificity. We have previously encapsulated EGCG into CSNLC carrying an oxidized LDL-derived ligand. This ligand has a high binding affinity to a macrophage scavenger receptor CD36 and should therefore participate in the receptor mediated recognition and uptake of CSNLC into aortic intimal macrophages. The novelty of this research is to encapsulate EGCG into biodegradable and biocompatible CSNLC, with the aims of 1) targeting to aortic intimal macrophages through surface modification using a target ligand; and 2) preventing and reversing the development of atherosclerosis in genetically susceptible LDL receptor null mice. To determine the specificity with which CSNLC-EGCG targets aortic intimal macrophages, cellular binding assay, cellular uptake of EGCG and oxidized LDL and inflammatory factor secretion levels will be measured in human macrophages derived from THP-1 monocytes. To determine the effects of CSNLC-EGCG on atherosclerosis in vivo, LDL receptor null mice will receive an atherogenic diet for 20 weeks. One experimental group will receive CSNLC-EGCG from week 1 until sacrifice, so that effects on the development of atherosclerosis can be observed. A second experimental group will receive CSNLC-EGCG from week 10 through week 20 so that effects on established atherosclerosis can be observed. A pathologist will evaluate the safety of EGCG and CSNLC in mice. This innovation portends a potential breakthrough in the prevention and treatment of atherosclerosis by using natural compounds with minimized immunogenicity and side-effects. The long-term goal of this line of research is to use biodegradable and biocompatible nanoparticles to increase bioavailability, solubility, stability and payload of therapeutic nutrients and natural compounds, lower their toxicity, prolong their circulation time, and target them to specific cells or tissues for disease prevention, diagnosis and treatment. PUBLIC HEALTH RELEVANCE: The proposed research will provide new insights and advance knowledge on nutraceuticals and chronic diseases, and have a wide range of potential applications in biomedical and health science. Attainment of enhanced stability, bioavailability and targeting through encapsulation of (-)-epigallocatechin gallate (EGCG) into biocompatible and biodegradable nanocarriers will open a new field in disease prevention and therapy of using natural compounds, representing a huge commercial market in the U.S. and abroad. The outcome is also expected to produce dramatic savings in the cost of medical care and improve the quality of life.

描述（由申请人提供）：动脉粥样硬化性心血管疾病是美国最常见的死亡原因。许多天然化合物显示出治疗这种严重疾病的希望，但它们在bdy中的低水平生物利用度和靶点特异性使得以治疗剂量施用它们不现实。这对于（-）-表没食子儿茶素没食子酸酯（EGCG）尤其如此，表没食子儿茶素没食子酸酯是在绿色茶中发现的天然化合物，其对于预防和治疗动脉粥样硬化是有价值的。本课题的目的是合成表没食子儿茶素没食子酸酯包封的壳聚糖包覆的纳米结构脂质载体（CSNLC-EGCG），以提高其稳定性、细胞生物利用度和对主动脉内膜巨噬细胞的靶向性，从而达到预防和逆转动脉粥样硬化病变的目的。主动脉内膜巨噬细胞是动脉粥样硬化病变发展的主要细胞。这些巨噬细胞摄取富含胆固醇的低密度脂蛋白（LDL），导致形成富含胆固醇的巨噬细胞（泡沫细胞），这是早期动脉粥样硬化病变的特征。表没食子儿茶素没食子酸酯能减少主动脉巨噬细胞中胆固醇的积聚，抑制泡沫细胞的形成，并减少主动脉巨噬细胞释放炎症因子。这些作用抑制动脉粥样硬化病变的发展，并可能促进动脉粥样硬化病变的消退。低水平的表没食子儿茶素没食子酸酯稳定性、生物利用度和靶向特异性阻止了这些益处的实现。 完全实现。迫切需要工程化的EGCG载体来增强其稳定性、细胞生物利用度和靶向特异性。我们之前已经将EGCG封装到携带氧化LDL衍生配体的CSNLC中。该配体对巨噬细胞清道夫受体CD 36具有高结合亲和力，因此应参与受体介导的CSNLC识别和摄取到主动脉内膜巨噬细胞中。本研究的新奇是将EGCG封装到可生物降解和生物相容的CSNLC中，目的是1）通过使用靶配体进行表面修饰靶向主动脉内膜巨噬细胞; 2）预防和逆转遗传易感性LDL受体缺失小鼠中动脉粥样硬化的发展。为了确定CSNLC-EGCG靶向主动脉内膜巨噬细胞的特异性，将在来源于THP-1单核细胞的人巨噬细胞中测量细胞结合测定、EGCG和氧化LDL的细胞摄取以及炎症因子分泌水平。为了确定CSNLC-EGCG对体内动脉粥样硬化的影响，LDL受体缺失小鼠将接受致动脉粥样硬化饮食20周。一个实验组将从第1周直到处死接受CSNLC-EGCG，以便可以观察对动脉粥样硬化发展的影响。第二个实验组将从第10周至第20周接受CSNLC-EGCG，以便可以观察对已建立的动脉粥样硬化的影响。病理学家将评估小鼠中EGCG和CSNLC的安全性。这项创新预示着通过使用具有最小免疫原性和副作用的天然化合物来预防和治疗动脉粥样硬化的潜在突破。该研究的长期目标是使用可生物降解和生物相容的纳米颗粒来增加治疗营养素和天然化合物的生物利用度，溶解度，稳定性和有效载荷，降低其毒性，延长其循环时间，并将其靶向特定细胞或组织用于疾病预防，诊断和治疗。 公共卫生相关性：拟议的研究将为营养保健品和慢性疾病提供新的见解和先进的知识，并在生物医学和健康科学中具有广泛的潜在应用。通过将（-）-表没食子儿茶素没食子酸酯（EGCG）包封到生物相容性和生物可降解的纳米载体中来实现增强的稳定性、生物利用度和靶向，将在使用天然化合物的疾病预防和治疗中开辟新的领域，在美国和国外代表巨大的商业市场。预计这一结果还将大大节省医疗费用，提高生活质量。

项目成果

Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals.

纳米技术在提高膳食植物化学物质的生物利用度和生物活性中的应用。

• DOI: 10.1016/j.jnutbio.2013.10.002
• 发表时间: 2014-04
• 期刊: The Journal of nutritional biochemistry
• 作者: Wang S;Su R;Nie S;Sun M;Zhang J;Wu D;Moustaid-Moussa N
• 通讯作者: Moustaid-Moussa N

Detection and treatment of atherosclerosis using nanoparticles.

• DOI: 10.1002/wnan.1412
• 发表时间: 2017-01
• 期刊: WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
• 影响因子: 8.6
• 作者: Zhang, Jia;Zu, Yujiao;Dhanasekara, Chathurika S.;Li, Jun;Wu, Dayong;Fan, Zhaoyang;Wang, Shu
• 通讯作者: Wang, Shu

Anti-atherogenic effects of CD36-targeted epigallocatechin gallate-loaded nanoparticles.

• DOI: 10.1016/j.jconrel.2019.04.018
• 发表时间: 2019-06
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Jia Zhang;Shufang Nie;Yujiao Zu;Mehrnaz Abbasi;Jun Cao;Chuan Li;Dayong Wu;S. Labib;G. Brackee;Chwan-Li Shen;Shu Wang

Nanoencapsulation enhances epigallocatechin-3-gallate stability and its antiatherogenic bioactivities in macrophages.

• DOI: 10.1021/jf4023004
• 发表时间: 2013-09-25
• 期刊: Journal of agricultural and food chemistry
• 影响因子: 6.1
• 作者: Zhang J;Nie S;Wang S
• 通讯作者: Wang S

Formulation, characteristics and antiatherogenic bioactivities of CD36-targeted epigallocatechin gallate (EGCG)-loaded nanoparticles.

• DOI: 10.1016/j.jnutbio.2015.11.001
• 发表时间: 2016-04
• 期刊: The Journal of nutritional biochemistry
• 作者: Zhang J;Nie S;Martinez-Zaguilan R;Sennoune SR;Wang S
• 通讯作者: Wang S