Silk Ionomer Biohybrid Nanoshells Integrating Fluorescent Nanodiamonds for Protective and Optically Responsive β‐Cell Interfaces

Protecting therapeutic cells while positioning optical probes at the cell-environment interface remains a major challenge in cell-based therapies. Here, we report a multifunctional biohybrid nanoshell combining conformal silk ionomer encapsulation with spatially localized fluorescent nanodiamond probes on pancreatic β-cell spheroids. Ultrathin coatings were constructed by electrostatic layer-by-layer assembly and incorporated carboxylated fluorescent nanodiamonds containing nitrogen-vacancy (NV) centers. This architecture enabled controlled placement of photostable optical probes while maintaining coating integrity. The coatings preserved spheroid metabolic activity and glucose-responsive insulin secretion. Incorporated nanodiamonds displayed pH-responsive optical behavior and were distinguished from the silk matrix and localized at the coated spheroid interface by fluorescence lifetime imaging. The transient silk nanoshell may provide early cytoprotection while minimizing long-term transport limitations. These findings demonstrate successful integration, spatial localization, and optical responsiveness of NV-containing nanodiamonds within an engineered cellular interface. However, quantitative sensing will require future spin-dependent measurements, including NV relaxometry or optically detected magnetic resonance. This platform provides a foundation for integrating protective cell-surface coatings with quantitative nanodiamond-based sensing in cell therapies.