Surface modification of live cells has important biomedical and therapeutic applications. Current methods to label cells require artificial cell surface engineering (via metabolic, docking or anchoring methods) before conjugative chemistries, which is not always trivial to accomplish and/or not appropriate for multiple cell types. A new method without the need of initial cell surface anchoring will greatly facilitate live cell surface labelling. Herein, we provide a general strategy for live cell functionalization that utilizes the native phosphate groups on every cell. We have designed a dual conjugation cargo molecule with a cationic side chain for non-covalent bonds with the negatively-charged cell surface and a phosphoric acid containing ligand for covalent bonding with the cell membrane phospholipid phosphate. Our dual conjugation strategy on live cell surfaces is non-toxic with enhanced stability to functionalize live cells. This provides a stable, reversible and reusable reagent with direct conjugation strategy to image live cell membranes.
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