Metal-Free Atom Transfer Radical Polymerization to Prepare Recylable Micro-Adjuvants for Dendritic Cell Vaccine
Hengyuan Zhang, Xingyu Heng, He Yang, Yu Rao, Lihua Yao, Zhichen Zhu,Gaojian Chen*(陈高健), Hong Chen*(陈红)
College of Chemistry, Chemical Engineering and Materials Science, Soochow University
Angew. Chem. Int. Ed. 2024, 63, e202402853
Abstract: In the development of dendritic cell (DC) vaccines, the maturation of DCs is a critical stage. Adjuvants play a pivotal role in the maturation of DCs, with a major concern being to ensure both efficacy and safety. This study introduces an innovative approach that combines high efficacy with safety through the synthesis of micro-adjuvants grafted with copolymers of 2-(methacrylamido) glucopyranose (MAG) and methacryloxyethyl trimethyl ammonium chloride (DMC). The utilization of metal-free surface-initiated atom transfer radical polymerization enables the production of safe and recyclable adjuvants. These micrometer-sized adjuvants surpass the optimal size range for cellular endocytosis, enabling the retrieval and reuse of them during the ex vivo maturation process, mitigating potential toxicity concerns associated with the endocytosis of non-metabolized nanoparticles. Additionally, the adjuvants exhibit a “micro-ligand-mediated maturation enhancement” effect for DC maturation. This effect is influenced by the shape of the particle, as evidenced by the distinct promotion effects of rod-like and spherical micro-adjuvants with comparable sizes. Furthermore, the porous structure of the adjuvants enables them to function as cargo-carrying “micro-shuttles”, releasing antigens upon binding to DCs to facilitate efficient antigen delivery.
链接://onlinelibrary.wiley.com/doi/10.1002/anie.202402853