Extracellular Vesicle Directed Exogenous Ion Channel Transport for Precise Manipulation of Biological Events

A larger number of human diseases are related to dysregulation or loss of cellular functions. Effective restoration of the missing or defective cellular functions is highly desirable for fundamental research and therapeutic applications. Inspired by the fantastic feature of cell-derived extracellular vesicles (EVs) that can transport various bioactive molecules between cells, herein, we developed a simple and efficient strategy based on EVs for transferring ion channels to recipient cells, thereby conferring specific biological function to the target cells and regulating the biological events. The constructed channel rhodopsin 2 (ChR2)-loaded EV (EV-ChR2) system can mediate the anchor of light-responsive ion channel ChR2 on the plasma membrane of recipient cells through membrane fusion. Upon blue light irradiation, the ion channel ChR2 was activated and opened, thus permitting the rapid flux of cation ions (e.g., calcium ion) across the plasma membrane of recipient cells. Moreover, the increased Ca²⁺ in the cytosol could effectively activate Ca²⁺-dependent transcription factors, further triggering the calcium signaling pathway. This strategy can be extended to modulate other cellular processes and provides a novel insight on the manipulation of biological events.