蛋白质定点原位可控聚合方法(SICP)的发展与应用

The Development and Application of Site-specific In situ Controlled Polymerization(SICP)

蛋白质-高分子偶联物是一类重要的长效化蛋白质,已被用于多种重大疾病的诊疗之中.探究新型、高效、温和的方法用以制备结构明确且功能可控的蛋白质-高分子偶联物是该领域所面对的重要科学问题.近年来,本课题组及同行将“蛋白质定点修饰”和“原位可控聚合”2种技术有机整合,提出了“蛋白质定点原位可控聚合”(site-specific in situ controlled polymerization,SICP)的方法,用以替代传统的聚乙二醇化技术,并在生物医学应用上取得了良好的进展.本专论主要从SICP方法的发展背景和内涵、蛋白质的定点修饰、原位可控聚合,以及SCIP在生物医学领域的应用等几个方面详细介绍SICP方法的研究进展,并对该方法未来的研发方向进行了简要的总结和展望.

Protein-polymer conjugates are an important class of long-acting proteins,and they have been applied in the diagnosis and treatment of various serious diseases.However,due to the shortcomings of non-specificity,low yield,and potential immunogenicity in current PEGylation method,exploring new,efficient,and mild methods for preparing protein-polymer conjugates with well-defined structures and controllable functions is an important scientific issue in this field.In recent years,our research group and colleagues integrated the two technologies of"site-specific protein modification"and"in situ controlled polymerization",proposing the concept of"site specific in situ controlled polymerization(SICP)"to replace traditional PEGylation technology,and made great progress in biomedical applications.The research progress of SICP method is introduced in detail in this review,which mainly focuses on the background of developing SICP methods,site-specific protein modification,in situ controlled polymerization,and its application in the biomedical fields.In the methodology part,the N-terminal site-specific modification method based on 2,6-pyridinedialdehyde and the in situ controllable polymerization method mediated by atom transfer radical polymerization(ATRP)are emphasized.In the biomedical application part,the applications of anti-tumor therapy,antibacterial therapy,and in vitro diagnosis are discussed,with a focus on the application of three different types of protein-polymer conjugates in anti-tumor therapy:self-assembled protein-polymer conjugates promoting protein pharmacokinetics,responsive protein-polymer conjugates enhancing tumor retention,and functional protein-polymer conjugates enhancing targeting efficiency and tumor permeability.Finally,brief summary and outlook on the future directions of developing SICP method are also discussed.