Sonoelectric Nanonet‐Activated Extracellular Electron Transfer for Wireless Non‐Genetic Stimulation of Pancreatic β Cells

Abstract Engineered cell‐based therapy is an emerging approach for treating intractable diseases, in which the remote control of cellular behavior necessitates robust physical input‐sensing‐response systems. Nanomaterials represent promising tools to enable wireless remote control of cells. To achieve this, the precise anchoring of nanomaterials to target cells is crucial for nanomaterial‐engineered cells to prevent undesired effects such as endocytosis and diffusion. Herein, we describe a general cell engineering strategy using nanomaterials to achieve remote‐controlled and sustained insulin release from the engineered pancreatic β cells. The prepared nanocomposite, termed TCN, is composed of defect‐rich titanium oxide quantum dots with ultrasound‐electric conversion effect and fibrous carbon substrate. In vitro experiments demonstrate that the TCN enables cell surface engineering through carbon substrate adsorption onto pancreatic β cells without chemical modification, while the TiO x quantum dots of TCN enable effective ultrasound‐responsive electrical stimulation to activate insulin release from β cells. Furthermore, we demonstrate that the subcutaneous implantation of TCN‐engineered β cell complexes in type 1 and type 2 diabetic mice enables the restoration of normoglycemia by ultrasound stimulation, establishing a nanomaterials‐enabled controlled cell therapy paradigm for diabetes.