Nature has evolved adaptive strategies to protect living cells and enhance their resilience against hostile environments, exemplified by bacterial and fungal spores. Inspired by cryptobiosis in nature, chemists have designed and synthesized artificial "cell-in-shell" structures, endowed with the protective and functional capabilities of nanoshells. The cell-in-shells hold the potential to overcome the inherent limitations of biologically naı̈ve cells, enabling the acquisition of exogenous phenotypic traits through the chemical process known as single-cell nanoencapsulation (SCNE). This review highlights recent advancements in the development of artificial spores, with sections organized based on the categorization of material types utilized in SCNE, specifically organic, hybrid, and inorganic types. Particular emphasis is placed on the cytoprotective and multifunctional roles of nanoshells, demonstrating potential applications of SCNEd cells across diverse fields, including synthetic biology, biochemistry, materials science, and biomedical engineering. Furthermore, the perspectives outlined in this review propose future research directions in SCNE, with the goal of achieving fine-tuned precision in chemical modulation at both intracellular and pericellular levels, paving the way for the design and construction of customized artificial spores tailored to meet specific functional needs.

Cell-in-shell biohybrid structures, synthesized by encapsulating individual living cells with exogenous materials, have emerged as exciting functional entities for engineered living materials, with emergent properties outside the scope of biochemical modifications. Artificial exoskeletons have, to date, provided physicochemical shelters to the cells inside in the first stage of technological development, and further advances in the field demand catalytically empowered, cellular hybrid systems that augment the biological functions of cells and even introduce completely new functions to the cells. This work describes a facile and generalizable strategy for empowering living cells with extrinsic catalytic capability through nanoencapsulation of living cells with a supramolecular metal-organic complex of Fe³⁺ and benzene-1,3,5-tricarboxylic acid (BTC). A series of enzymes are embedded in situ, without loss of catalytic activity, in the Fe³⁺ -BTC shells, not to mention the superior characteristics of cytocompatible and rapid shell-forming processes. The nanoshell enhances the catalytic efficiency of multienzymatic cascade reactions by confining reaction intermediates to its internal voids and the nanoencapsulated cells acquire exogenous biochemical functions, including enzymatic cleavage of lethal octyl-β-d-glucopyranoside into d-glucose, with autonomous cytoprotection. The system will provide a versatile, nanoarchitectonic tool for interfacing biological cells with functional materials, especially for catalytic bioempowerment of living cells.