The cell membrane acts not only as a physical barrier but also as a functional organelle that regulates communication between cells and their environment. Functionalizing the cell membrane using synthetic molecules or nanostructures has the potential to enhance cellular functions beyond those achieved through natural evolution. Cell therapy represents a groundbreaking approach in treating major challenging diseases, including tissue injuries, degenerative diseases, and congenital metabolic disorders. The primary focus of biomedical research has always been on regulating cellular functions to maximize the efficiency of cell therapy.

Given that the cell surface plays a critical role in cellular physiology and pathology by controlling recognition and communication between cells and their environment, functionalizing the cell surface emerges as an effective method for regulating cellular functions. A range of cell surface modification techniques have been developed based on molecular self-assembly approaches, wherein exogenous biomolecules and biomaterials are constructed on the cell surface through molecular engineering to regulate cell function and enhance the efficacy of cell therapy. This non-genetic engineering-based modification of the cell surface can functionalize cells within hours, significantly reducing manufacturing costs and processes without genetically modifying the cells, thereby making transient manipulation of cell functions feasible while avoiding potential safety risks.

The highly specific biotin-avidin interaction exhibits remarkable resistance to harsh denaturing conditions, including heat, pH fluctuations, and organic solvents. Consequently, biotinylation holds immense promise in cell surface engineering. Cell surface-based biotinylation modification, leveraging the strong affinity between biotin molecules and avidin, enables the specific introduction of biotin on the cell surface, thereby functionalizing the cell through biotin-avidin binding.

This technology typically involves the following steps:

Introduction of biotin linker: Initially, molecules containing biotin linker groups must be introduced onto the cell surface. This can be accomplished through various methods, such as employing compounds containing biotin or utilizing biotin ligase to catalyze the covalent binding of biotin to cell surface molecules.

Covalent binding of biotin linker with cell surface molecules: The biotin linker forms covalent bonds with molecules on the cell surface, thereby introducing biotin onto the cell membrane. This binding is typically highly specific, enabling the selective modification of specific cell surface structures.

Interaction between biotin and avidin: Once the cell surface is labeled with biotin, the high -affinity interaction between biotin and avidin is utilized to functionalize the cell. Avidin is usually associated with fluorescent labels, polymers, or other molecular tags, which, upon specific binding with biotin, are introduced onto the cell surface, achieving functional modification of the cell.

Functional application: Following the labeling of the cell surface with biotin and its binding to avidin, various functional modifications of the cell can be achieved. For instance, fluorescent labels can be utilized for cell imaging, drug carriers can be attached to the cell surface for drug delivery, or other functional molecules can be employed to regulate cell signaling, among other applications.

Utilizing cell membrane coating technology to enhance the efficacy of drugs involves introducing additional cell membrane functions to increase their specificity. Although cell membrane-coated nanoparticles (CM-NPs) can achieve prolonged circulation, adding targeting ligands can enhance their localization to specific targets, such as tumors. This cell membrane-based ligand modification technology offers a simpler and more effective approach by combining natural cell membranes with different ligands for biological tasks.

This strategy involves stabilizing functional ligand molecules on the extracellular domains of cell membrane proteins using cell-impermeable linkers. The crux of this method lies in coupling the ligand with cell membrane proteins, thereby achieving functional modification of the cell membrane. This cell membrane-based surface engineering technology offers drug delivery systems with enhanced specificity and targeting, particularly in fields like tumor therapy, with extensive application prospects.