Dampening autoimmunity with encapsulated autoantigens in polyphenolic capsules

用多酚胶囊中封装的自身抗原抑制自身免疫

• 批准号: 1608728
• 负责人: Eugenia Kharlampieva
• 金额: $ 42万
• 依托单位: University of Alabama at Birmingham
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1608728&HistoricalAwards=false
• 关键词: Dampening; autoimmunity; encapsulated; autoantigens; polyphenolic

Nontechnical: This award by the Biomaterials program in the Division of Materials Research to University of Alabama at Birmingham is to develop biologically-active biomaterials for potential treatment of an autoimmune disease, such as Type 1 diabetes (T1D). Restoring immune tolerance, i.e., the inability of the immune system to respond to specific autoantigens such as insulin is a major challenge in T1D. To address this challenge, this project will develop novel immunoprotective polymeric nano- and micro-particles with encased insulin to dampen aberrant Type 1 diabetes autoimmune responses. This research will impact the design and application of a new type of polymer material with autoimmune modulating activity and will provide a fundamental understanding of the physical and chemical properties of these materials at biological interfaces. The design of this material will open new prospects in various bio-related areas such as bioengineering and tissue engineering and autoimmune therapies. The educational objective of this project is to develop a discovery-driven multidisciplinary biomaterials/polymer sciences program at University of Alabama at Birmingham in promoting diversity from the high school through graduate-level. These students, including underrepresented minorities, will be trained in modern aspects of biopolymer sciences including state-of-the-art synthetic and analytical methods, and they will take part in intensive multidisciplinary collaborations between the Departments of Chemistry and Microbiology. Technical: The goal of this proposal is to develop a new type of immunomodulatory particulate material with encased autoantigens (insulin) for dampening autoimmune responses in Type 1 diabetes (T1D), and to gain a fundamental understanding of the mechanism of immune modulating activity. These hollow particles will be designed through hydrogen-bonded assemblies of polyphenolic tannic acid (TA) with neutral polymers to produce micro- and nano-capsules for delivery of insulin to immune cells and restore their immune tolerance. The objectives of the proposed study are as follows: 1) synthesis TA-based microcapsules with novel temperature-sensitive diblock copolymers, and explore their immune cell uptake properties; 2) explore the loading of insulin into capsules with tunable thermal, antioxidant and anti-inflammatory properties; 3) investigate immunomodulation of antigen-presenting cells with TA-based capsules with dampening autoimmune responses in an autoantigen-specific manner; and 4) study the interaction of these materials with antigen-presenting cells in vitro. Correlations between material physical/chemical properties and function of immune cells is pivotal for transformative knowledge in developing immunomodulatory materials for treating a broad spectrum of autoimmune diseases. Access to state-of-the-art techniques with unique capabilities of in situ nano-scaled measurements, advanced imaging, and immunology facilities will ensure the successful completion of the project. Recruitment and/or mentoring of students at different levels - High school, undergraduate, and graduate including underrepresented minorities - and training them in modern aspects of biopolymer sciences including state-of-the-art synthetic and analytical methods are parts of this award.

非技术性：该奖项由材料研究部生物材料项目授予伯明翰亚拉巴马大学，旨在开发生物活性生物材料，用于治疗自身免疫性疾病，如1型糖尿病（T1 D）。恢复免疫耐受，即，免疫系统不能对特异性自身抗原如胰岛素作出反应是T1 D的主要挑战。为了应对这一挑战，该项目将开发新型免疫保护性聚合物纳米和微米颗粒，包裹胰岛素，以抑制异常的1型糖尿病自身免疫反应。这项研究将影响具有自身免疫调节活性的新型聚合物材料的设计和应用，并将提供对这些材料在生物界面的物理和化学性质的基本了解。这种材料的设计将在生物工程和组织工程以及自身免疫治疗等各种生物相关领域开辟新的前景。 该项目的教育目标是在伯明翰的亚拉巴马大学开发一个以发现为驱动的多学科生物材料/聚合物科学项目，以促进从高中到研究生水平的多样性。这些学生，包括代表性不足的少数民族，将接受生物聚合物科学的现代方面的培训，包括最先进的合成和分析方法，他们将参加化学和微生物学部门之间的密集多学科合作。技术支持：该提案的目标是开发一种新型的免疫调节颗粒材料，其中包含包裹的自身抗原（胰岛素），用于抑制1型糖尿病（T1 D）的自身免疫反应，并对免疫调节活性的机制有基本的了解。这些中空颗粒将通过多酚单宁酸（TA）与中性聚合物的氢键组装来设计，以产生微胶囊和纳米胶囊，用于将胰岛素递送到免疫细胞并恢复其免疫耐受性。 本论文的主要研究内容如下：1）合成新型温敏性二嵌段共聚物TA微囊，并探讨其免疫细胞摄取特性; 2）探索胰岛素在热、抗氧化和抗炎特性可调的微囊中的负载; 3）研究用基于TA的胶囊以自身抗原特异性方式抑制自身免疫应答对抗原呈递细胞的免疫调节;（4）体外研究这些材料与抗原呈递细胞的相互作用。 材料物理/化学性质与免疫细胞功能之间的相关性对于开发用于治疗广谱自身免疫性疾病的免疫调节材料的变革性知识至关重要。 获得最先进的技术，具有独特的原位纳米级测量能力，先进的成像和免疫学设施将确保该项目的成功完成。招聘和/或指导不同层次的学生-高中，本科和研究生，包括代表性不足的少数民族-并在生物聚合物科学的现代方面对他们进行培训，包括最先进的合成和分析方法。