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

基本信息

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
项目类别：
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

项目摘要

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）：动脉粥样硬化心血管疾病是美国最常见的死亡原因。许多天然化合物表现出有望弥补这种严重疾病的希望，但是它们在BDY中的生物利用度和目标特异性水平较低，使其以治疗剂量不现实进行给药。对于（ - ） - 绿茶中的天然化合物（EGCG）（EGCG）尤其如此，这对于预防和治疗动脉粥样硬化很有价值。该项目的目的是合成EGCG封装的壳聚糖涂层的纳米结构脂质载体（CSNLC-EGCG），以提高其稳定性，细胞生物利用度和靶向性的水平，并靶向主动脉衰减巨噬细胞，以防止和反转动脉粥样硬化性疾病。主动脉内膜巨噬细胞是负责动脉粥样硬化病变发育的主要细胞。这些巨噬细胞会占据富含胆固醇的低密度脂蛋白（LDL），导致形成胆固醇巨噬细胞（泡沫细胞），这表征了早期的动脉粥样硬化病变。 EGCG可以减少主动脉巨噬细胞中胆固醇的积累，抑制泡沫细胞的形成，并减少从主动脉巨噬细胞中释放的炎症因子。这些作用抑制了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。 EGCG稳定性，生物利用度和目标特异性的低水平阻止了这些收益完全意识到。设计的EGCG载体非常需要增强其稳定性，细胞生物利用度和目标特异性。我们以前已经将EGCG封装在带有氧化LDL衍生配体的CSNLC中。该配体与巨噬细胞清道夫受体CD36具有很高的结合亲和力，因此应参与受体介导的识别和摄取CSNLC进入主动脉内膜巨噬细胞。这项研究的新颖性是将EGCG封装到可生物降解和生物相容性的CSNLC中，其目的是通过靶配体通过表面修饰来靶向主动脉内膜巨噬细胞； 2）防止和逆转基因易感的LDL受体无小鼠的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，细胞结合测定，EGCG的细胞摄取和氧化的LDL的细胞摄取以及炎症因子分泌水平将在从THP-1单细胞中得出的人类巨噬细胞中测量。为了确定CSNLC-EGCG对体内动脉粥样硬化的影响，LDL受体无效小鼠将接受动脉粥样硬化饮食20周。一个实验组将从第1周从牺牲开始接收CSNLC-EGCG，因此可以观察到对动脉粥样硬化发展的影响。从第10周到第20周，第二个实验组将接收CSNLC-EGCG，以便可以观察到对已建立的动脉粥样硬化的影响。病理学家将评估EGCG和CSNLC在小鼠中的安全性。这种创新预示着通过使用具有最小的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。这项研究线的长期目标是使用可生物降解和生物相容性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，并将其靶向预防疾病，诊断和治疗的特定细胞或组织。公共卫生相关性：拟议的研究将提供新的见解，并提高有关营养疾病和慢性疾病的知识，并在生物医学和健康科学中具有广泛的潜在应用。通过封装（ - ） - epigallocatechin Gallate（EGCG）将增强的稳定性，生物利用度和靶向靶向，并将可生物降解的纳米载体纳入疾病预防和使用自然化合物的疾病预防和疗法的新领域，代表美国和非洲的巨大商业市场。预计结果还可以节省医疗费用并改善生活质量。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
作者：
Wang S;Su R;Nie S;Sun M;Zhang J;Wu D;Moustaid-Moussa N
通讯作者：
Moustaid-Moussa N

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
影响因子：
0
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
通讯作者：
Jia Zhang;Shufang Nie;Yujiao Zu;Mehrnaz Abbasi;Jun Cao;Chuan Li;Dayong Wu;S. Labib;G. Brackee;Chwan-Li Shen;Shu Wang

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

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