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

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. [Graphics] .