Endocytosis-like vesicle fission by membrane-expanding molecular machine enabling virus encapsulation for in vivo delivery

Since the cellular process of endocytosis enables uptake of biomacromolecules interacting with the cell surface by outside-in vesicle fission, endocytosis-like membrane deformation is an ideal methodology for the incorporation of micrometer-size biomacromolecules into vesicles. However, such endocytosis-like vesicle fission, which requires expansion of the liposomal membrane, has never been realized using artificial liposomal systems. Here, we developed a membrane-expanding molecular machine containing a diazocine core (AzoMEx), which exhibits an opening/closing mechanical motion in response to visible light. Upon blue light irradiation, AzoMEx embedded in a 1,2-dioleoyl-sn-glycero-3-phosphocholine bilayer expanded the liposomal membrane, assembled, and eventually induced outside-in endocytosis-like fission. When this vesicle fission was induced in the presence of micrometer-size M13 phage, it was efficiently incorporated into the vesicle by interacting with AzoMEx. The encapsulated M13 phage was transiently protected from the external environment, retaining its biological activity, and thus could be distributed throughout the body after blood administration.