蛋白质定点原位可控聚合方法(SICP)的发展与应用

刘欣宇; 高卫平

doi:10.11777/j.issn1000-3304.2023.23088

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蛋白质定点原位可控聚合方法(SICP)的发展与应用

专论 | 更新时间：2023-09-25

- 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)
- 高分子学报 2023年54卷第10期页码：1395-1408
- 作者机构：
  
  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
- 作者简介：
  
  [ "高卫平，男，1975年生. 1993~2000年，青岛化工学院，高分子工程专业本科与硕士；2000~2004年，北京大学，高分子化学与物理专业，博士. 曾先后在日本京都大学化学研究所和美国杜克大学生物医学工程系从事博士后研究，现任北京大学跨学部生物医学工程系长聘副教授，博士生导师. 曾任清华大学医学院生物医学工程系研究员，博士生导师. 在PNAS、JACS、Angew Chem、Adv Mater等国际知名期刊上发表论文50余篇，研究成果多次被Nature、Science China Materials和Genetic Engineering & Biotechnology News专题报道，曾获Bayer Investigator Award、Janssen Investigator Award、清华大学优秀博士学位论文指导教师奖. 主要研究方向为生物材料与药物递送." ]
- 基金信息：
  
  国家重点研发计划(2022YFC2405900;2022YFC2405903);国家自然科学基金(基金号 ┣82202327);21534006┫;北京市科技新星计划(Z211100002121013)
- DOI：10.11777/j.issn1000-3304.2023.23088
  中图分类号：
- 纸质出版日期：2023-10-20，
  
  网络出版日期：2023-06-16，
  
  收稿日期：2023-04-01，
  
  录用日期：2023-04-28
扫描看全文
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.

摘要

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.

Abstract

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.

关键词

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

Keywords

Protein-polymer conjugatesSite-specific in situ controlled polymerizationAtom transfer radical polymerizationAnti-tumor therapyStimuli-responsiveness

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