Surface modification of live cells has many biological applications including imaging, control of cell surface interactions, tracking and sensing biological environments in vitro and in vivo. Over the years, several methods such as chemo-selective conjugation, PEGylation etc. have been extensively explored to modify cell surfaces with various cargos/therapeutic agents via non-covalent interactions (between positively-charged polyelectrolytes and negatively-charged cell surfaces) and covalent interactions (bonding between cargos and the functional groups on cell surfaces). However, problems remain for both non-covalent interaction based conjugation of cell surface modification, as well as, covalent conjugation of surfaces based on unnatural chemical reactions. Conjugates of cell surfaces via non covalent interactions show limited time stability. On the other hand, covalent conjugation via unnatural chemical reactions provides longer stability, but these reactions are not cytocompatible with mammalian cells due to toxicity from metal catalysed chemical modification of membrane proteins. Recently, cell membranes were conjugated with well-engineered therapeutic loaded nanoparticles but they cannot be used in vivo due to toxicity resulting from entrapment in the reticuloendothelial system of the liver and spleen. We have these addressed two challenges, namely, cytocompatible with mammalian cell membranes and stable conjugation for long time in live cells. We have designed a cargo molecule with a cationic side chain which will form non-covalent bond with the negatively charged cell surface and a phosphoric acid containing ligand which will facilitate phosphor-ester covalent bonding with the cell membrane phosphate functionality as separate bio-orthogonal reactions. Infact, conjugation of our well designed cargo with T-cells show cytocompatibility and stability of the surface conjugation for a long period of time in varying pH (5.5 to 8.5) conditions. We believe our dual-conjugation approach will provide a stable technology for imaging and cellular sensing with live cells.

Live cell surface conjugation methods for imaging and sensing

255th National Meeting (2018)

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