Bioempowerment of Therapeutic Living Cells by Single‐Cell Surface Engineering

Abstract Living cells have the irreplaceable capability to achieve a wide range of complex biochemical reactions precisely and efficiently, which makes them attractive materials for therapeutic applications. In lieu of the traditional biochemical and biological approaches primarily focused on the augmentation of the innate functions of cells, there has been appreciable progress in the development of engineered therapeutic cells, mainly based on the chemical modifications of cell surfaces, at the single‐cell level, which empowers individual living cells with designed therapeutic functions in a cytocompatible manner. This review highlights the latest advances in the development of therapeutic living cells using single‐cell surface engineering, for potential applications in blood transfusion, drug delivery, cancer therapy, probiotic therapy, and tissue engineering and regenerative medicine. The methodological strategies for functionalizing cell surfaces with biomolecules, and inorganic and organic materials, to endow living cells with extrinsic physicochemical and biological properties as well as to increase the durability and efficacy of engineered therapeutic cells, are also briefly overviewed. The review ends with a perspective that discusses the construction of active cell‐in‐shell nanobiohybrid systems, in which exogenous materials formed on cell surfaces mutually and intimately communicate with the cells inside, as a future research direction for single‐cell surface engineering.