The cytoprotective coating of physicochemically labile mammalian cells with a durable material has potential applications in cell-based sensors, cell therapy, and regenerative medicine, as well as providing a platform for fundamental single-cell studies in cell biology. In this work, HeLa cells in suspension were individually coated with silica in a cytocompatible fashion through bioinspired silicification. The silica coating greatly enhanced the resistance of the HeLa cells to enzymatic attack by trypsin and the toxic compound poly(allylamine hydrochloride), while suppressing cell division in a controlled fashion. This bioinspired cytocompatible strategy for single-cell coating was also applied to NIH 3T3 fibroblasts and Jurkat cells.

Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-Fe(III) nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-Fe(III) nanocoat, mimicking the sporulation and germination processes found in nature.

Single-cell nanoencapsulation, forming cell-in-shell structures, provides chemical tools for endowing living cells, in a programmed fashion, with exogenous properties that are neither innate nor naturally achievable, such as cascade organic-catalysis, UV filtration, immunogenic shielding, and enhanced tolerance in vitro against lethal factors in real-life settings. Recent advances in the field make it possible to further fine-tune the physicochemical properties of the artificial shells encasing individual living cells, including on-demand degradability and reconfigurability. Many different materials, other than polyelectrolytes, have been utilized as a cell-coating material with proper choice of synthetic strategies to broaden the potential applications of cell-in-shell structures to whole-cell catalysis and sensors, cell therapy, tissue engineering, probiotics packaging, and others. In addition to the conventional "one-time-only" chemical formation of cytoprotective, durable shells, an approach of autonomous, dynamic shellation has also recently been attempted to mimic the naturally occurring sporulation process and to make the artificial shell actively responsive and dynamic. Here, the recent development of synthetic strategies for formation of cell-in-shell structures along with the advanced shell properties acquired is reviewed. Demonstrated applications, such as whole-cell biocatalysis and cell therapy, are discussed, followed by perspectives on the field of single-cell nanoencapsulation.

Single‐cell nanoencapsulation is an emerging field in cell‐surface engineering, emphasizing the protection of living cells against external harmful stresses in vitro and in vivo. Inspired by the cryptobiotic state found in nature, cell‐in‐shell structures are formed, which are called artificial spores and which show suppression or retardation in cell growth and division and enhanced cell survival under harsh conditions. The property requirements of the shells suggested for realization of artificial spores, such as durability, permselectivity, degradability, and functionalizability, are demonstrated with various cytocompatible materials and processes. The first‐generation shells in single‐cell nanoencapsulation are passive in the operation mode, and do not biochemically regulate the cellular metabolism or activities. Recent advances indicate that the field has shifted further toward the formation of active shells. Such shells are intimately involved in the regulation and manipulation of biological processes. Not only endowing the cells with new properties that they do not possess in their native forms, active shells also regulate cellular metabolism and/or rewire biological pathways. Recent developments in shell formation for microbial and mammalian cells are discussed and an outlook on the field is given.

S. cerevisiae encapsulated with a poly(norepinephrine)/silica double-layered shell showed multiple resistance to enzymatic attack, desiccation, and UV-C irradiation. The biochemical response of the encapsulated yeast may also contribute to the UV-C resistance.