Restuccia Antonietta, Fettis Margaret M, Hudalla Gregory A
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
J Mater Chem B. 2016 Mar 7;4(9):1569-1585. doi: 10.1039/c5tb01780g. Epub 2015 Oct 22.
Synthetic materials that can engage the innate and adaptive immune systems are receiving increasing interest to confer protection against onset of future disease, such as pathogen infection, as well as to treat established diseases, such as autoimmunity and cancer. Carbohydrates are integral to various immune-related processes, including inflammation, adaptive memory, and tolerance, through both their non-covalent recognition of carbohydrate-binding proteins and as chemical signatures that distinguish self from non-self. Harnessing the biological activity of carbohydrates, however, was long hindered by the lack of a 'sugar code' defining their structure-function relationships, the difficulty of carbohydrate synthesis, and the weak binding affinity of monovalent carbohydrates for proteins or other biomolecules. The advent of new glycan synthesis approaches, combined with increased understanding of the role of multivalent carbohydrate clusters in immunology, has spurred significant recent growth in the development of multivalent synthetic materials modified with carbohydrates (i.e."glycomaterials") to activate, temper, or inhibit specific immunological processes. In this review, we highlight recent advances in glycomaterials that can inhibit T cell apoptosis, establish antigen-specific tolerance, suppress inflammation, or inhibit viral entry into host cells via non-covalent recognition of carbohydrate-binding proteins. In addition, we survey glycomaterials that can act as vaccines for adaptive immunological recognition and memory of carbohydrate antigens, with a particular emphasis on vaccines against tumor-associated carbohydrate antigens as cancer immunotherapies. In total, these examples demonstrate the enormous potential of glycomaterials to prevent or treat diverse diseases by engaging specific immunological processes.
能够激活先天性和适应性免疫系统的合成材料正越来越受到关注，这类材料不仅可以预防未来疾病的发生，如病原体感染，还可以治疗已有的疾病，如自身免疫性疾病和癌症。碳水化合物在各种免疫相关过程中不可或缺，包括炎症、适应性记忆和免疫耐受，这是通过它们与碳水化合物结合蛋白的非共价识别以及作为区分自我与非自我的化学标记来实现的。然而，由于缺乏定义其结构 - 功能关系的 “糖代码”、碳水化合物合成的困难以及单价碳水化合物与蛋白质或其他生物分子的弱结合亲和力，碳水化合物生物活性的利用长期以来受到阻碍。新的聚糖合成方法的出现，加上对多价碳水化合物簇在免疫学中作用的深入理解，最近极大地推动了用碳水化合物修饰的多价合成材料（即 “糖材料”）的发展，以激活、调节或抑制特定的免疫过程。在这篇综述中，我们重点介绍了糖材料的最新进展，这些糖材料可以通过与碳水化合物结合蛋白的非共价识别来抑制T细胞凋亡、建立抗原特异性耐受、抑制炎症或抑制病毒进入宿主细胞。此外，我们还综述了可以作为碳水化合物抗原适应性免疫识别和记忆疫苗的糖材料，特别强调了作为癌症免疫疗法的针对肿瘤相关碳水化合物抗原的疫苗。总的来说，这些例子证明了糖材料通过参与特定免疫过程来预防或治疗多种疾病的巨大潜力。
