A Micrometric Transformer: Compositional Nanoshell Transformation of Fe3+ -Trimesic-Acid Complex with Concomitant Payload Release in Cell-in-Catalytic-Shell Nanobiohybrids.

Nanoencapsulation of living cells within artificial shells is a powerful approach for augmenting the inherent capacity of cells and enabling the acquisition of extrinsic functions. However, the current state of the field requires the development of nanoshells that can dynamically sense and adapt to environmental changes by undergoing transformations in form and composition. This paper reports the compositional transformation of an enzyme-embedded nanoshell of Fe3+ -trimesic acid complex to an iron phosphate shell in phosphate-containing media. The cytocompatible transformation allows the nanoshells to release functional molecules without loss of activities and biorecognition, while preserving the initial shell properties, such as cytoprotection. Demonstrations include the lysis and killing of Escherichia coli by lysozyme, and the secretion of interleukin-2 by Jurkat T cells in response to paracrine stimulation by antibodies. This work on micrometric Transformers will benefit the creation of cell-in-shell nanobiohybrids that can interact with their surroundings in active and adaptive ways.

Fugetaxis of Cell-in-Catalytic-Coat Nanobiohybrids in Glucose Gradients.

Manipulation and control of cell chemotaxis remain an underexplored territory despite vast potential in various fields, such as cytotherapeutics, sensors, and even cell robots. Herein is achieved the chemical control over chemotactic movement and direction of Jurkat T cells, as a representative model, by the construction of cell-in-catalytic-coat structures in single-cell nanoencapsulation. Armed with the catalytic power of glucose oxidase (GOx) in the artificial coat, the nanobiohybrid cytostructures, denoted as Jurkat[Lipo_GOx] , exhibit controllable, redirected chemotactic movement in response to d-glucose gradients, in the opposite direction to the positive-chemotaxis direction of naïve, uncoated Jurkat cells in the same gradients. The chemically endowed, reaction-based fugetaxis of Jurkat[Lipo_GOx] operates orthogonally and complementarily to the endogenous, binding/recognition-based chemotaxis that remains intact after the formation of a GOx coat. For instance, the chemotactic velocity of Jurkat[Lipo_GOx] can be adjusted by varying the combination of d-glucose and natural chemokines (CXCL12 and CCL19) in the gradient. This work offers an innovative chemical tool for bioaugmenting living cells at the single-cell level through the use of catalytic cell-in-coat structures.