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.

Advancing cell surface modification in mammalian cells with synthetic molecules

“…12 One notable example is the universal blood, which involves the modification of red blood cell surfaces to impede the recognition of antigenic sites by antibodies, thereby preventing immune responses caused by blood type incompatibility. 13–15 Chemical manipulation of cell behavior and function through modification of cell surfaces using precisely synthesized and well-characterized synthetic molecules, such as polymers, is a captivating area of research. 16 Various strategies have been devised for this purpose.…”

Subcellular Nanobionic Liposome with High Zeta Potential Enhances Intravesical Adhesion and Drug Delivery

“…The construction of biocompatible assemblies that are capable of chemical communication and cross-talk at the subcellular scale of living interfaces is a significant challenge for synthetic biology. , A natural cell membrane-inspired assembly strategy provides an excellent opportunity to synthesize carriers in the form of liposomes. , Such assemblies offer considerable advantages for drug delivery and biomedical applications. , The properties of liposomal architecture are regulated by size, charge, lipid composition, and surface modification with polymers or ligands. , For example, cholesterol can stabilize the membrane and protect it from leakage in the circulation. − Intravesical drug delivery can increase drug uptake while reducing systemic toxicity in diabetic bladder dysfunction (DBD). , However, the anatomical structure of the urothelial layer makes it difficult for passively ingested liposomes to communicate with living cells and tissue barriers, and they are easily washed out. , Therefore, improving cross-talk at the living interface is critical for drug and carrier penetration into bladder tissues.…”

“…1,2 A natural cell membraneinspired assembly strategy provides an excellent opportunity to synthesize carriers in the form of liposomes. 3,4 Such assemblies offer considerable advantages for drug delivery and biomedical applications. 5,6 The properties of liposomal architecture are regulated by size, charge, lipid composition, and surface modification with polymers or ligands.…”