短肽自组装水凝胶的温和制备方法及免疫佐剂应用

Short Peptide-based Hydrogels: Mild Preparation Methods and Their Application as Vaccine Adjuvant

短肽自组装水凝胶是一种新型的软物质材料,它由短肽通过自组装形成,具有生物活性和生物相容性高、易于设计与合成以及对外部刺激能快速响应等优点,它在生物医药、分析检测、组织工程等领域有很高的应用前景.本文主要总结了我们近年来在短肽自组装水凝胶温和制备方法研发方面的工作,同时介绍了短肽自组装水凝胶在疫苗佐剂方面的创新应用,并探讨了短肽自组装水凝胶研究领域的挑战及研究热点.

Self-assembly prevails in nature, and has been used as a powerful strategy for construction of functional materials. Small molecular hydrogel is composed of nanofibers formed by self-assembly of small molecules（molecular weight usually 2000） in aqueous solution. Among them, hydrogels formed by the self-assembly of short peptides through noncovalent interaction have attracted intensive interests due to their ease of design, bi℃ompatibility and biodegradability, as well as fast response to external environment. Several classical methods have been developed to construct peptide-based hydrogels, including heating-cooling cycle, p H value adjustment, ionic strength change, solvent transform and sonication induction. However, these methods were not suitable for the encapsulation of bioactive components such as proteins and cells. Therefore, more bi℃ompatible methods were needed for the biomedical application of peptide-based hydrogels. This paper summarizes our recent work on the development of bi℃ompatible and mild preparation methods for the peptide-based hydrogels, including enzymatic triggeration, disulfide bond cleavage, redox control and specific protein-peptide interaction inducement. These strategies showed benefits for biomedical applications of short peptide-based hydrogels, including drug delivery, analyte detection, cancer inhibition and regenerative medicine. Recently, pioneering works demonstrated that self-assembled peptides could be used as self-adjuvated vaccines through covalent conjugation of peptide or protein antigens. We found several peptide-based hydrogels that could elicit strong immune responses by simply mixing them with antigens, which showed distinct advantages over other commercially available immune adjuvants. We summarize in this review a simple strategy to deliver subunit vaccines by physically mixing antigens including DNA, protein, and attenuated cells with nanofibers of self-assembling peptides. Vaccines based on self-assembling peptides can raise stronger antibody productions, which is useful for protective vaccine development and antibody production. Besides, several vaccines capable of eliciting strong CD8＋ T cell response are also introduced, and they are promising for the development of vaccines to treat important diseases such as cancers and HIV. Challenges remained are also mentioned in the last section of this review. Overall, self-assembling peptides are very useful for antibody production and the development of novel vaccines to treat important diseases.