Dampening autoimmunity with encapsulated autoantigens in polyphenolic capsules

非技术领域：该奖项由阿拉巴马大学伯明翰分校材料研究部生物材料项目颁发，旨在开发具有生物活性的生物材料，用于治疗自身免疫性疾病，如1型糖尿病（T1D）。恢复免疫耐受，即免疫系统无法对特定自身抗原（如胰岛素）做出反应，是T1D的主要挑战。为了应对这一挑战，该项目将开发新型的免疫保护聚合物纳米和微粒，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上的物理和化学性质的基本理解。该材料的设计将在生物工程、组织工程和自身免疫治疗等生物相关领域开辟新的前景。该项目的教育目标是在阿拉巴马大学伯明翰分校建立一个以发现为导向的多学科生物材料/聚合物科学项目，以促进从高中到研究生阶段的多样性。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现代方面的培训，包括最先进的合成和分析方法，他们将参与化学和微生物学系之间的多学科合作。技术：本提案的目标是开发一种新型的免疫调节颗粒材料，内含自身抗原（胰岛素），用于抑制1型糖尿病（T1D）的自身免疫反应，并对免疫调节活性的机制有一个基本的了解。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合来设计，以生产微胶囊和纳米胶囊，用于将胰岛素输送到免疫细胞并恢复其免疫耐受性。本研究的目的是：1)合成具有新型温度敏感双嵌段共聚物的ta基微胶囊，并探索其免疫细胞摄取特性；2)探索将胰岛素装入具有可调热、抗氧化和抗炎特性的胶囊中；3)研究以ta为基础的胶囊通过自身抗原特异性方式抑制自身免疫反应对抗原提呈细胞的免疫调节作用；4)在体外研究这些材料与抗原提呈细胞的相互作用。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泛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尺度测量能力，先进的成像和免疫学设施将确保项目的成功完成。招募和/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，这是该奖项的一部分。

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.