Liu Xiangquan, Wang Youyu, Ye Bangce, Bi Xiaobao
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology Hangzhou 310014 Zhejiang China
Lab of Biosystem and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology Shanghai 200237 China
Chem Sci. 2023 Jun 8;14(26):7334-7345. doi: 10.1039/d3sc01382k. eCollection 2023 Jul 5.
Although numerous genetic, chemical, and physical strategies have been developed to remodel the cell surface landscape for basic research and the development of live cell-based therapeutics, new chemical modification strategies capable of decorating cells with various genetically/non-genetically encodable molecules are still urgently needed. Herein, we describe a remarkably simple and robust chemical strategy for cell surface modifications by revisiting the classical thiazolidine formation chemistry. Cell surfaces harbouring aldehydes can be chemoselectively conjugated with molecules containing a 1,2-aminothiol moiety at physiological pH without the need to use any toxic catalysts and complicated chemical synthesis. Through the combined use of thiazolidine formation and the SpyCatcher-SpyTag system, we have further developed a SpyCatcher-SpyTag Chemistry Assisted Cell Surface Engineering (SpyCASE) platform, providing a modular approach for the construction of large protein-cell conjugates (PCCs) in their native state. Thiazolidine-bridged molecules can also be detached from the surface again through a biocompatible Pd-catalyzed bond scission reaction, enabling reversible modification of living cell surfaces. In addition, this approach allows us to modulate specific cell-cell interactions and generate NK cell-based PCCs to selectively target/kill several EGFR-positive cancer cells . Overall, this study provides an underappreciated but useful chemical tool to decorate cells with tailor-made functionalities.
尽管已经开发了许多遗传、化学和物理策略来重塑细胞表面景观，用于基础研究和基于活细胞的治疗方法的开发，但仍然迫切需要能够用各种遗传/非遗传可编码分子修饰细胞的新化学修饰策略。在此，我们通过重新审视经典的噻唑烷形成化学，描述了一种用于细胞表面修饰的极其简单且稳健的化学策略。在生理pH条件下，含有醛的细胞表面可以与含有1,2-氨基硫醇部分的分子进行化学选择性共轭，而无需使用任何有毒催化剂和复杂的化学合成。通过联合使用噻唑烷形成和SpyCatcher-SpyTag系统，我们进一步开发了一种SpyCatcher-SpyTag化学辅助细胞表面工程（SpyCASE）平台，为构建天然状态的大型蛋白质-细胞缀合物（PCC）提供了一种模块化方法。噻唑烷桥连的分子也可以通过生物相容性钯催化的断键反应再次从表面脱离，实现活细胞表面的可逆修饰。此外，这种方法使我们能够调节特定的细胞-细胞相互作用，并生成基于NK细胞的PCC，以选择性地靶向/杀死几种EGFR阳性癌细胞。总体而言，这项研究提供了一种未被充分认识但有用的化学工具，用于用定制功能修饰细胞。
