Polymerization‐Mediated Multifunctionalization of Living Cells for Enhanced Cell‐Based Therapy

TLDR

Surface decoration of living cells by exogenous substances offers a unique tool for understanding and tuning cell behaviors, which plays a critical role in cell‑based therapy. Here, a facile yet versatile approach for decorating individual living cells with multimodal coatings is reported. By simply co‑depositing with dopamine under a cytocompatible condition, various functional small molecules and polymers can be encoded to form a multifunctional coating on a cell's surface. The method successfully decorates diverse cells—including bacteria, fungi, and mammalian cells—producing ligand‑coated gut microbiota that exhibit over 30‑fold higher gut bioavailability and four‑fold greater accumulation in inflamed tissue, outperforming uncoated bacteria and clinical aminosalicylic acid in colitis mice, thereby establishing a robust platform for multimodal cell‑based therapy.

Abstract

Abstract Surface decoration of living cells by exogenous substances offers a unique tool for understanding and tuning cell behaviors, which plays a critical role in cell‐based therapy. Here, a facile yet versatile approach for decorating individual living cells with multimodal coatings is reported. By simply co‐depositing with dopamine under a cytocompatible condition, various functional small molecules and polymers can be encoded to form a multifunctional coating on a cell's surface. The accessibility and versatility of this method to decorate diverse cells, including bacteria, fungi, and mammalian cells is demonstrated. With the ability to tune surface functions, ligand co‐deposited gut microbiota is prepared as oral therapeutics for targeted treatment of colitis. Given the dual cytoprotective and targeting effects of the coating, decorated cells show more than 30‐times higher bioavailability in the gut and fourfold higher accumulation in the inflamed tissue in comparison with those of uncoated bacteria. Multimodal therapeutic cells further validate strikingly increased treatment efficacy over clinical aminosalicylic acid in colitis mice. Decorating with multifunctional coatings proposes a robust platform for developing multimodal cells for enhanced cell‐based therapy.