Single-Cell Nanoencapsulation: Chemical Synthesis of Artificial Cell-in-Shell Spores

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.