Encapsulating living cells within nanoshells offers an important approach to enhance their stability against environmental stressors and broaden their application scope. However, this often leads to impaired mass transfer at the cell biointerface. Strengthening the protective shell with well-defined, ordered transport channels is crucial to regulating molecular transport and maintaining cell viability and biofunctionality. Herein, we report the construction of covalent organic framework (COF) mesoporous shells for single-cell nanoencapsulation, providing selective permeability and comprehensive protection for living microbial cells. The COF shells ensure nutrient uptake while blocking large harmful molecules and UV-C radiation, thereby preserving cell viability and metabolic activity. Integration of such crystalline porous shells with genetically modified cell factories for metabolic production is further investigated, revealing no adverse effects, as demonstrated by riboflavin production. Moreover, the COF shell effectively shields cells, ensuring efficient bioproduction even after being treated under harsh conditions. This versatile encapsulation approach is applicable for different cell types, providing a robust platform for cell surface engineering.
Keywords: covalent organic frameworks; cytoprotection; microbial cell factories; porous materials; single-cell nanoencapsulation.