Single-cell nanoencapsulation

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Single-cell nanoencapsulation (SCNE) is an interdisciplinary research field at the intersection of chemistry, biology, nanoscience, and materials science. Single-cell nanoencapsulation involves the development and application of nanometer-scaled shells for the isolation, protection, and functionalization of individual living cells.^[1][2][3][4] Single-cell nanoencapsulation enables the fundamental studies of cell–material interactions at the single-cell level, and supports research and development across a range of applied fields, including cell therapy, renewable energy, regenerative medicine, probiotics, and agricultural innovation. By controlling the cellular microenvironment at the nanoscale, single-cell nanoencapsulation allows for fine-tuned investigation of individual cell responses and the design of engineered cellular systems with tailored properties.

Single-cell nanoencapsulation is also a chemical strategy that creates "cell-in-shell" structures by forming artificial nanoshells (typically <100 nm in thickness) on individual cells.^[5] The cell-in-shell structures are referred to by various names depending on the context or application, including artificial spores,^[6][7] cyborg cells, Supracells, micrometric Iron Men, and micrometric Transformers.

Single-cell nanoencapsulation is considered complementary or, in some contexts superior to, cell microencapsulation techniques.^[8][9][10] Single-cell nanoencapsulation enables precise modulation and control of cellular behavior at the single-cell level by encapsulating individual cells within artificial nanoshells composed of organic, inorganic, or hybrid materials.^[1]

The term "SCNE" is also used as a verb in scientific literature, with phrases such as "SCNEd cells" referring to the cells that have undergone the process of single-cell nanoencapsulation.^[11]

Nanoshell properties for artificial spores have been proposed:^[2][6][7]

• durability: The nanoshell should be mechanically and (bio)chemically robust, capable of withstanding external stresses such as osmotic pressure and dehydration while preserving its structure. The durability could also enable control over cell growth and division by resisting internal biological forces.
• permselectivity: The porosity of the artificial shell should be chemically tunable to allow the selective exchange of small molecules—such as gases and nutrients—while blocking harmful agents like lytic enzymes and macrophages, thereby supporting cell viability.
• degradability: The shell should be designed to degrade on demand in a stimulus-responsive manner. Controlled chemical breakdown enables the restoration or activation of the nanoencapsulated cell's biological functions after chemical germination.
• functionalizability: The nanoshell should allow for chemical modification either during or after formation without compromising cell viability, enabling functional augmentation as well as specific recognition and interaction with the external environment.