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1.北京大学,口腔医学院,北京 100081
2.北京大学,跨学部生物医学工程系,北京 100081
Published:20 October 2023,
Published Online:16 June 2023,
Received:01 April 2023,
Accepted:28 April 2023
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刘欣宇,高卫平.蛋白质定点原位可控聚合方法(SICP)的发展与应用[J].高分子学报,2023,54(10):1395-1408.
Liu Xin-yu,Gao Wei-ping.The Development and Application of Site-specific In situ Controlled Polymerization (SICP)[J].ACTA POLYMERICA SINICA,2023,54(10):1395-1408.
刘欣宇,高卫平.蛋白质定点原位可控聚合方法(SICP)的发展与应用[J].高分子学报,2023,54(10):1395-1408. DOI: 10.11777/j.issn1000-3304.2023.23088.
Liu Xin-yu,Gao Wei-ping.The Development and Application of Site-specific In situ Controlled Polymerization (SICP)[J].ACTA POLYMERICA SINICA,2023,54(10):1395-1408. DOI: 10.11777/j.issn1000-3304.2023.23088.
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.
蛋白质-高分子偶联物定点原位可控聚合方法原子转移自由基聚合抗肿瘤治疗刺激响应性
Protein-polymer conjugatesSite-specific in situ controlled polymerizationAtom transfer radical polymerizationAnti-tumor therapyStimuli-responsiveness
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