Abstract
Re-engineering mammalian cell surfaces enables modulation of their phenotype, function, and interactions with external markers and may find application in cell-based therapies. Here we use metabolic glycan labeling to install azido groups onto the cell surface, which can act as anchor points to enable rapid, simple, and robust “click” functionalization by the addition of a polymer bearing orthogonally reactive functionality. Using this strategy, new cell surface functionality was introduced by using telechelic polymers with fluorescence or biotin termini, demonstrating that recruitment of biomacromolecules is possible. This approach may enable the attachment of payloads and modulation of cell function and fate, as well as providing a tool to interface synthetic polymers with biological systems.
Highlights
Cell-based therapies are potent tools in modern medicine, from blood transfusions and bone marrow transplants, to rapidly emerging treatments such as stem cell and CAR-T therapy.[1−4] these cells are limited in their native functionality and phenotype
Synthetic polymer− protein conjugates have shown significant success in improving therapeutic efficacy by increasing stability, circulation half-lives and storage.[5]. Such benefits have made PEGylated (poly(ethyene glycol)-grafted) proteins the gold standard in the pharmaceutical industry.[6−10] Covalent polymer reformulation of cell-based therapies is the frontier to aid translation, add non-natural functionality, such as imaging agents and/or loading of additional cargo, and to improve logistics.[11−13] re-engineering of mammalian cell surfaces with synthetic polymers is a valuable tool for biomedicine and biotechnology
Polymer-coated islet cells have been the subject of study to mask cell-surface antigens, minimizing graft rejection in xenogeneic and allogenic transplants, while retaining biological function.[14−19] Cell PEGylation methods used to achieve this include N-hydroxy succinimide and biotin.[20−23] PEGylated erythrocytes can improve blood transfusion compatibility by blocking AB antigens, while reducing malaria parasite binding and preventing diseases characterized by impaired blood flow or vaso-occlusion.[24−28] Despite cellsurface engineering holding great promise, challenges remain in the design of clinical-translatable and effective methods
Summary
Cell-surface glycans play major metabolic, structural, and recognition roles in biology. We wanted to demonstrate that additional functionality can be brought to the cell surface using these polymers while retaining availability of the nongrafted chain end (and not sterically limited by, for example, the glycocalyx) This approach enables encoding of additional information to the cell surface without using genetic engineering. Due to the increased loading of the DP50 polymers, there was approximately double (values in Supporting Information) the recruitment extent of streptavidin compared to DP100 This model system demonstrates the versatility of this method to re-engineer cells with non-native functionality using accessible and versatile tools. Experimental procedures and characterization data, plus additional binding experiments (PDF)
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