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

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.