Efficient and rapid cell surface functionalization: a sub-minute selenol-yne click reaction for bioconjugation

Cell surface engineering plays a crucial role in enhancing the functionality and therapeutic potential of living cells through precise and controllable surface modifications. However, traditional conjugation strategies often suffer from limited efficiency or inherent complexity. In this work, we developed a selenol-yne click (SYC) reaction for efficient and rapid cell surface functionalization, enabling covalent attachment of diverse payloads to a variety of cell types. The SYC reaction enables highly efficient conjugation of fluorescent molecules, micron-scale "backpack" particles, and functional polymers onto cell surfaces, including HeLa, B16-OVA, and Jurkat T cells. Drug-loaded backpacks carried by the cells demonstrated effective drug delivery to target cells. Moreover, cell surface glycosylation via this method enables efficient modulation of cell-cell interactions and immune responses. Importantly, glycosylation was also successfully achieved in living zebrafish through the SYC reaction, demonstrating its potential for in vivo applications. This SYC-based strategy offers a fast and versatile platform for advancing cell surface engineering.